US11512116B2 - Chimeric receptor binding proteins for use in bacterial delivery vehicles - Google Patents

Chimeric receptor binding proteins for use in bacterial delivery vehicles Download PDF

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US11512116B2
US11512116B2 US17/527,754 US202117527754A US11512116B2 US 11512116 B2 US11512116 B2 US 11512116B2 US 202117527754 A US202117527754 A US 202117527754A US 11512116 B2 US11512116 B2 US 11512116B2
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Jesus Fernandez Rodriguez
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Eligo Bioscience
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Definitions

  • This application includes an electronically submitted sequence listing in .txt format.
  • the .txt file contains a sequence listing entitled “2643-3 US TRK-1_ST25.txt” created on Mar. 9, 2020 and is 940,581 bytes in size.
  • the sequence listing contained in this .txt file is part of the specification and is hereby incorporated by reference herein in its entirety.
  • the present disclosure relates generally to bacterial delivery vehicles for use in efficient transfer of a desired payload into a target bacterial cell. More specifically, the present disclosure relates to bacterial delivery vehicles with desired host ranges based on the presence of a chimeric receptor binding protein (RBP) composed of a fusion between the N-terminal region of a RBP derived from a lambda-like, or lambda bacteriophage and the C-terminal region of a different RBP.
  • RBP chimeric receptor binding protein
  • Bacteriophages are parasites that infect and multiply in bacteria.
  • the infection process can be divided in several stages: (i) adsorption corresponding to recognition and binding to the bacterial cell; (ii) injection of the DNA genome into the bacterial cell cytoplasm; (iii) production of a set of viral proteins that can lead to insertion in the host target genome (lysogenic phages) or to the production of infective particles (lytic phages) and (iv) release of mature virions from the infected cell, usually by controlled lysis [1].
  • Bacteriophages Being the first step necessary for a successful infection, recognition and binding to the target cell is an essential process in the bacteriophage life cycle. Bacteriophages can in some cases recognize several strains of the same species, having a “broad host range”, but very commonly are able to recognize a specific antigen present only on some strains of the same species [2]. It is thus not surprising that this step of the infection process is central in the competition between bacteriophage and bacteria for successful infection.
  • a bacteriophage encodes two main sets of proteins that are involved in the recognition process.
  • the first set is able to attach to the bacteriophage's primary receptor on the cell surface, an event that triggers DNA ejection into the cytoplasm and is usually viewed as an “irreversible” binding process [3].
  • Different bacteriophage genera differ in the organization of this set of proteins, and hence the naming can be different.
  • they are called the “central tail fiber” or “tail tip”, which binds irreversibly to the LamB receptor in Escherichia coli .
  • the “central tail fiber” or “tail tip” is composed of the protein gpJ [4].
  • Siphovirus like T5
  • a protein located at the very tip of the tail mediates this process.
  • pb5 recognizes the FhuA receptor [5]. This type of protein can be found in many other bacteriophages.
  • Myoviruses like T4, the irreversible binding to the primary receptor or to the cell surface in general is mediated by the “short tail fibers”, which are also located at the end of the tail tube [5].
  • the second set of proteins in the bacteriophage (herein referred to as “receptor binding proteins”) encodes recognition and binding activities to the so-called “secondary receptor” on the bacterium.
  • This secondary receptor allows for transient binding of the phage particle on the cell surface in order to scan the surface and position the first set of proteins in contact with the primary receptor. Since this binding is reversible, it allows the phage to “walk” on the cell surface until a primary receptor is found and the infection process starts.
  • These protein complexes are sometimes referred to as “L-shape fibers”, such as in T5, “side tail fibers” such as in lambda, “long tail fibers” as in T4, or tailspikes such as in phage P22 [5]-[8].
  • this second set of proteins is necessary for the infection process to occur, such as T4 [5].
  • this second set of proteins is not strictly necessary for the infection process to happen, but it may allow for a more efficient binding to the target cell [7].
  • bacteria can develop multiple ways to avoid being recognized by a bacteriophage. For example, they can mutate the primary or secondary receptor to which the bacteriophage binds; they can mask this receptor by attaching proteins to it (receptor masking); or they can grow physical barriers around them in the form of bacterial capsules, thus blocking any access to the cell surface [9]. Bacteria can produce many different types of extracellular polymeric capsules [10]. In turn, bacteriophages have evolved different strategies to bypass these defense mechanisms. For instance, mutating the tail tip proteins allows them to use a different receptor [11].
  • a bacteriophage's host range needs to be redefined when only the adsorption and injection processes are taken into account. Since all incompatibilities or defense mechanisms related to the phage replication cycle are left out of the picture, the “adsorption host range” of a given phage is usually larger than the “classical host range” in which the infectious cycle leads to newly produced mature virions. The concept of host range becomes even more different to the classical definition when packaged phagemids based on a given bacteriophage capsid is used. Packaged phagemids do not contain the information necessary to replicate the viral particles, because they do not package their cognate viral genome.
  • the host range of a packaged phagemid tends to be larger than that of the parental bacteriophage it derives from. Therefore, for development of novel bacterial delivery vehicles, designed for the efficient delivery of exogenous DNA payload into target strains, it is of utmost importance to be able to engineer delivery vehicles with desired host ranges as well as the ability to bypass bacterial mechanisms that can lead to unsuccessful binding of the packaged phagemid to the bacterial cell surface.
  • a bacteriophage encodes sets of proteins that are involved in the bacterial cell recognition process. Described herein are novel approaches to engineering synthetic bacterial delivery vehicles with desired target host ranges.
  • synthetic bacterial delivery vehicles are provided that are characterized by a chimeric receptor binding protein (RBP), wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different bacteriophage RBP.
  • RBP chimeric receptor binding protein
  • Such bacteriophage RBPs include, for example, and depending on phages families, “L-shape fibers”, “side tail fibers (stfs)”, “long tail fibers” or “tailspikes.”
  • a lambda-like bacteriophage receptor binding protein such as a stf protein
  • RBP lambda-like bacteriophage receptor binding protein
  • the chimeric receptor binding protein is one wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal RBP with reference to the lambda stf sequence (SEQ ID NO: 1) or a similar region of a RBP having homology with one or more of three amino acid regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda stf sequence.
  • the different RBP domain of the chimeric receptor binding protein (RBP) is derived from any bacteriophage or from any bacteriocin
  • the RBP from the lambda-like bacteriophage, or the lambda bacteriophage, or the different RBP contains homology in one or more of three amino acid regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1).
  • the homology between the lambda-like bacteriophage, the lambda bacteriophage, or the different RBP and the one or more of three amino acids regions is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, and around 90% identity for 18 amino acids or more with reference to the lambda bacteriophage stf sequence (SEQ ID NO:1). Determination of homology can be performed using alignment tools such as the Smith-Waterman algorithm (Smith et al., 1981, J. Mol. Biol 147:195-197) or EMBOSS Matcher (Rice, Longden, Bleasby 2000 EMBOSS Trends in Genetics 16: 276-277).
  • the chimeric RBP comprises the N-terminal domain of a RBP fused to the C-terminal domain of a different RBP within one of the amino acid regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO:1).
  • the chimeric RBP comprises an N-terminal domain and a C-terminal domain fused within one of the amino acids regions selected from positions 1-150, 320-460 or 495-560 at an insertion site having at least 80% identity with an insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO: 248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251) and, GAGENS (SEQ ID NO: 252).
  • the chimeric RBP comprises the N-terminal domain of a RBP fused to the C-terminal domain of different RBP wherein the different RBP is a protein or group a different proteins that confers an altered host range.
  • the different RBP is a T4-like or T4 long tail fiber composed of a proximal tail fiber and a distal tail fiber (DTF), and the C-terminal domain of a T4-like or T4 RBP is the distal tail fiber (DTF).
  • the N-terminal domain of a RBP is fused to the T4-like or T4 distal tail fiber at an insertion site within the T4-like or T4 DTF having at least 80% identity with an insertion site selected from the group consisting of amino acids ATLKQI (SEQ ID NO: 253), IIQLED (SEQ ID NO: 254), GNIIDL (SEQ ID NO: 255), IATRV (SEQ ID NO: 256), TPGEL (SEQ ID NO: 257), GAIIN (SEQ ID NO: 258), NQIID (SEQ ID NO: 259), GQIVN (SEQ ID NO: 260) and, VDRAV (SEQ ID NO: 261).
  • the N-terminal domain of a RBP is fused to the T4-like or T4 distal tail fiber within a region from amino acid 1 to 90, with a preferred region from amino acid 40 to 50 of the DTF.
  • the disclosure provides specific chimeric RBPs.
  • SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs as well as, in some instances, their corresponding natural chaperone proteins (designated “AP”). Such AP proteins assist in the folding of the chimeric RBPs.
  • the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 123-129, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246.
  • nucleotide sequences encoding for the chimeric RBPs disclosed herein are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210 and 212-213.
  • the nucleic acids encoding such chimeric RBPs comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172 175, 182, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
  • the different RBP domain of the chimeric RPB comprises depolymerase activity against an encapsulated bacterial strain.
  • the depolymerase is an endosialidase such as, for example, a K1F or K5 endosialidase.
  • nucleic acid molecules encoding the chimeric RBPs disclosed herein are provided.
  • Such nucleic acids may be included in vectors such as bacteriophages, plasmids, phagemids, viruses, and other vehicles which enable transfer and expression of the chimeric RBP encoding nucleic acids.
  • Bacterial delivery vehicles are provided which enable transfer of a nucleic acid payload, encoding a protein or nucleic acid of interest, into a desired target bacterial host cell.
  • Such bacterial delivery vehicles are characterized by having a chimeric RBP comprising a fusion between the N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and the C-terminal domain of a different RBP.
  • the bacterial delivery vehicles contain a chimeric RBP comprising a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal domain with reference to the lambda stf sequence (SEQ ID NO: 1).
  • the RBP from the lambda-like bacteriophage, the lambda bacteriophage, and the different RBP contain homology in one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1).
  • the homology is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, or around 90% identity for 18 amino acids or more within the one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence.
  • the different RBP domain of the chimeric receptor binding protein is derived from a bacteriophage or a bacteriocin.
  • the chimeric RBP comprises an N-terminal domain of a RBP fused to a C-terminal domain of a RBP within one of the amino acids regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP domain with reference to the lambda stf sequence.
  • the chimeric RBP comprises an N-terminal domain of a RBP and a C-terminal domain of a RBP fused within a site of the N-terminal RBP domain having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO: 248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
  • the disclosure provides a bacterial delivery vehicle comprising a chimeric RBP.
  • SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs and in addition, in some instances, their corresponding natural chaperone proteins (designated “AP”). Such AP proteins assist in the folding of the chimeric RBPs.
  • the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 130, 131, 132, 135, 138, 139, 142, 145, 148,151, 216, 219, 221, 223, 227, 230, 232, 234,236, 238, 240, 243, 245 or 246.
  • the present disclosure also provides nucleotide sequences encoding for the chimeric RBPs disclosed herein.
  • nucleic acids encoding such chimeric RBPs, as well as corresponding AP proteins are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210 and 212-213.
  • the nucleic acids encoding such chimeric RBPs comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172, 175, 182, 185, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
  • the different RBP domain of the chimeric RBP comprises a domain having depolymerase activity against an encapsulated bacterial strain.
  • the depolymerase is an endosialidase, such as for example, a K1F or K5 endosialidase.
  • the bacterial delivery vehicles provided herein enable transfer of a nucleic acid payload, encoding one or more protein or nucleic acid of interest, into a desired target bacterial host cell.
  • the nucleic acid of interest is selected from the group consisting of a Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme such as a nuclease or a kinase, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor, a membrane protein, a structural protein, a secreted protein, a gene expressing resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any of their combination.
  • the nucleic acid payload encodes a therapeutic protein. In another embodiment, the nucleic acid payload encodes an anti-sense nucleic acid molecule. In some embodiment, the nucleic acid payload encodes 2 nucleic acid of interest, one being a nuclease gene, for instance a Cas nuclease gene, and one being any other nucleic acid of interest.
  • the bacterial delivery vehicle enables the transfer of a nucleic acid payload that encodes a nuclease that targets cleavage of a host bacterial cell genome or a host bacterial cell plasmid. In some aspects, the cleavage occurs in an antibiotic resistant gene. In another embodiment of the invention, the nuclease mediated cleavage of the host bacterial cell genome is designed to stimulate a homologous recombination event for insertion of a nucleic acid of interest into the genome of the bacterial cell.
  • the present invention also provides pharmaceutical or veterinary compositions comprising one or more of the bacterial delivery vehicles disclosed herein and a pharmaceutically-acceptable carrier. Also provided is a method for treating a bacterial infection comprising administering to a subject having a bacterial infection in need of treatment the provided pharmaceutical or veterinary composition. A method for reducing the amount of virulent and/or antibiotic resistant bacteria in a bacterial population is provided comprising contacting the bacterial population with the bacterial delivery vehicles disclosed herein.
  • FIG. 1 demonstrates delivery in wild-type E. coli strains with lambda and OMPF-lambda packaged phagemids.
  • Lambda packaged phagemids were diluted 1:5 in LB plus 5 mM CaCl2 and 10 uL added in each well. 90 uL of cells grown to an OD600 of around 0.5 were then added to each phagemid-containing well, incubated for 30 min at 37° C. and 10 uL spotted on LB-agar supplemented with chloramphenicol.
  • Left panel wild type lambda packaged phagemids; right panel, OMPF-lambda variant. Arrows show strains with modified delivery as compared to lambda wild-type.
  • FIG. 2 depicts wild-type lambda and lambda-stf-K1F chimeric delivery vehicles on K1+strains.
  • Lambda packaged phagemids were sequentially diluted 10 ⁇ in LB plus 5 mM CaCl2 and 10 uL added in each well. Cells grown to an OD600 of around 0.5 were then added to each phagemid dilution, incubated for 30 min at 37° C. and 10 uL plated on LB supplemented with chloramphenicol.
  • Top panel strain UTI89; bottom panel, strain S88. Left plates, wild type lambda packaged phagemids; right plates, stf-K1F lambda packaged phagemids.
  • FIG. 3 depicts wild-type lambda and lambda-stf-K5 chimeric delivery vehicles on a K5+ strain.
  • Lambda packaged phagemids were sequentially diluted 10 ⁇ in LB plus 5 mM CaCl2 and 10 uL added in each well.
  • ECOR55 grown to an OD600 of around 0.5 were then added to each phagemid dilution, incubated for 30 min at 37° C. and 10 uL plated on LB supplemented with chloramphenicol.
  • Left panel wild type lambda packaged phagemids
  • right panel stf-K15 lambda packaged phagemids.
  • FIG. 4 depicts wild-type lambda, lambda-stf-AG22 and lambda-stf-SIEA11 chimeric delivery vehicles on a variety of encapsulated strains (O and K capsules).
  • Lambda phagemids were diluted 1:5 in LB plus 5 mM CaCl2 and 10 uL added in each well. 90 uL of cells grown to an OD600 of around 0.5 were then added to each phagemid-containing well, incubated for 30 min at 37° C. and 10 uL spotted on LB-agar supplemented with chloramphenicol.
  • FIG. 5A-C demonstrates delivery of wild-type lambda and stf chimeras with different insertion sites on a variety of encapsulated strains (0 and K capsules).
  • Lambda packaged phagemids were diluted 1:5 in LB plus 5 mM CaCl2 and 10 uL added in each well. 90 uL of cells grown to an OD600 of around 0.5 were then added to each phagemid-containing well, incubated for 30 min at 37° C. and 10 uL spotted on LB-agar supplemented with chloramphenicol.
  • FIG. 5(A) Left panel, wild type lambda packaged phagemids; rest of panels, three different ADAKKS-stf variants.
  • FIG. 5(B) Left panel, wild type lambda packaged phagemids; rest of panels, three different SASAAA-stf variants.
  • FIG. 5(C) Left panel, wild type lambda packaged phagemids; rest of panels, three different MDETNR-stf variants. For all panels, arrows show strains with improved delivery efficiency as compared to lambda wild-type.
  • FIG. 6 depicts a phmmer search that was performed with a 50aa sliding window (step 10) on the representative proteome database (rp75). The number of significant hits (E-value ⁇ 0.01) is reported.
  • FIG. 7 depicts architecture of the engineered lambda stf-T4-like DTF chimera.
  • the semicircles denote RBS sites; the T sign, a transcriptional terminator; the arrow, a promoter.
  • FIG. 8 shows screening of phagemid particles with chimeric lambda stf-T4-like DTFs.
  • Left panel wild-type lambda stf; middle panel, chimeric lambda-stf-WW13; right panel, chimeric lambda-stf-PP-1.
  • FIG. 9 demonstrates screening of phagemid particles with chimeric lambda stf-T4-like DTFs.
  • Left panel wild-type lambda stf; middle panel, chimeric lambda-stf-WW55; right panel, chimeric lambda-stf-WW34.
  • FIG. 10 depicts screening of phagemid particles with chimeric lambda stf-T4-like DTFs. All points shown refer to the universal insertion site of the DTF, located within aminoacid range from position 1 to 90 with reference to WW13 aminoacid sequence.
  • FIG. 11 depicts dot scoring system to quantify delivery efficiency. Density 0, 5 or fewer colonies; density 1, more than 5 colonies but not enough to define a clear circular drop; density 2, several colonies, but the background is clearly visible and some colonies are still separated; density 3, many colonies, the background is still visible but the colonies are hardly discernible as separate; density 4, spot almost completely dense, the background can only be seen faintly in some parts of the drop; density 5, spot looks completely dense, background cannot be seen.
  • FIG. 12-1 , FIG. 12-2 , and FIG. 12-3 depicts raw dot titrations of delivery particles with chimeric stf in 40 human strains of the ECOR collection. Below each panel, the name of the chimeric stf. Above each dot, the 1-2 letter code used to identify strains in FIG. 13 .
  • the synthetic bacterial delivery vehicles are characterized by a chimeric receptor binding protein (RBP), wherein the chimeric RBP comprises a fusion between the N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and the C-terminal domain of a different RBP.
  • RBP chimeric receptor binding protein
  • a receptor binding protein or RBP is a polypeptide that recognizes, and optionally binds and/or modifies or degrades a substrate located on the bacterial outer envelope, such as, without limitation, bacterial outer membrane, LPS, capsule, protein receptor, channel, structure such as the flagellum, pili, secretion system.
  • the substrate can be, without limitation, any carbohydrate or modified carbohydrate, any lipid or modified lipid, any protein or modified protein, any amino acid sequence, and any combination thereof.
  • a lambda-like bacteriophage refers to any bacteriophage encoding a RBP having amino acids sequence homology of around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, or around 90% identity for 18 amino acids or more in one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 with reference to the lambda bacteriophage stf sequence of SEQ ID NO: 1, independently of other amino acids sequences encoded by said bacteriophage.
  • the present disclosure provides a chimeric receptor binding protein (RBP), wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different bacteriophage RBP.
  • RBP chimeric receptor binding protein
  • Such bacteriophage RBPs include, for example, “L-shape fibers”, “side tail fibers (stfs)”, “long tail fibers” or “tailspikes.”
  • a lambda-like bacteriophage receptor binding protein such as a stf protein
  • RBP lambda-like bacteriophage receptor binding protein
  • stf protein a stf protein
  • specific fusion positions in the RBPs have been identified which allow one to obtain a functional chimeric RBP.
  • Such chimeric RBPs include those having an altered host range and/or biological activity such as, for example, depolymerase activity.
  • the chimeric receptor binding protein is one wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal RBP with reference to the lambda stf sequence (SEQ ID NO: 1) or a similar region of a RBP having homology with one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda stf sequence.
  • the different RBP of the chimeric receptor binding protein (RBP) is derived from any bacteriophage or from any bacteriocin.
  • the RBP from the lambda-like bacteriophage, the lambda bacteriophage, or the different RBP contain homology with one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO:1).
  • the homology between the lambda-like bacteriophage, the lambda bacteriophage, or the different RBP and the one or more amino acids regions is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, and around 90% identity for 18 amino acids or more.
  • the chimeric RBP comprises the N-terminal domain of the chimeric RBP fused to the C-terminal domain of the chimeric RBP within one of the amino acids regions selected from positions 80-150, 320-460, or 495-560 with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1).
  • the chimeric RBP comprises an N-terminal domain and a C-terminal domain fused within one the three amino acids regions at an insertion site having at least 80% identity with an insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO: 248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
  • the invention provides chimeric RBPs.
  • SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs and in addition, in some instances, their corresponding natural chaperone proteins (designated “AP”).
  • AP proteins assist in the folding of the chimeric RBPs.
  • the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234,236, 238, 240, 243, 245 or 246
  • the present disclosure also provides nucleotide sequences encoding for the chimeric RPBs disclosed herein.
  • nucleic acids encoding such chimeric RBPs, as well as corresponding AP proteins are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210, 212-213.
  • the nucleic acids encoding the chimeric RBP comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172, 175 182, 185, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
  • the different RBP domain of the chimeric RPB comprises depolymerase activity against an encapsulated bacterial strain.
  • the depolymerase is an endosialidase such as, for example, a K1F or K5 endosialidase.
  • Nucleic acid molecules encoding the chimeric RBPs disclosed herein are provided. Such nucleic acids may be included in vectors such as bacteriophages, plasmids, phagemids, viruses, and other vehicles which enable transfer and expression of the chimeric RBP encoding nucleic acids.
  • Bacterial delivery vehicles are provided which enable transfer of a nucleic acid payload, encoding a protein or nucleic acid of interest, into a desired target bacterial host cell.
  • Such bacterial delivery vehicles are characterized by having a chimeric RBP comprising a fusion between the N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and the C-terminal domain of a different RBP.
  • the bacterial delivery vehicles contain a chimeric RBP comprising a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal domain RBP with reference to the lambda stf sequence (SEQ ID NO: 1).
  • the RBP from the lambda-like bacteriophage, the lambda bacteriophage, and the different RBP contain homology in one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the N-terminal RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1).
  • the homology is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, or around 90% identity for 18 amino acids or more within the one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the N-terminal RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1).
  • the different RBP domain of the chimeric receptor binding protein (RBP) is derived from a bacteriophage or a bacteriocin.
  • the chimeric RBP comprises an N-terminal domain of a RBP fused to a C-terminal domain of a RBP within one of the amino acids regions selected from 80-150, 320-460, or 495-560 of the RBPs with reference to the lambda stf sequence (SEQ ID NO: 1).
  • the chimeric RBP comprises an N-terminal domain of a RBP and a C-terminal domain of a RBP fused within a site of the N-terminal RBPs having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO. 248), ADAKKS (SEQ ID NO. 249), MDETNR (SEQ ID NO. 250), SASAAA (SEQ ID NO. 251), and GAGENS (SEQ ID NO. 252).
  • the disclosure provides a bacterial delivery vehicle comprising a chimeric RBP.
  • SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs and in addition, in some instances, their corresponding natural chaperone proteins (designated “AP”). Such AP proteins assist in the folding of the chimeric RBPs.
  • the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 130, 131, 132, 135, 138, 139, 142, 145, 148 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246
  • the present disclosure also provides nucleotide sequences encoding for the chimeric RPBs disclosed herein.
  • nucleic acids encoding such chimeric RBPs, as well as corresponding AP proteins are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210, 212-213.
  • the nucleic acids encoding the chimeric RBPs comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172, 175, 182, 185, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
  • the different RBP domain of the chimeric comprises a domain having depolymerase activity against an encapsulated bacterial strain.
  • the depolymerase is an endosialidase, such as for example, a K1F or K5 endosialidase.
  • the bacterial delivery vehicles provided herein enable transfer of a nucleic acid payload, encoding a protein or nucleic acid of interest, into a desired target bacterial host cell.
  • delivery vehicle refers to any means that allows the transfer of a payload into a bacterium.
  • delivery vehicles encompassed by the present invention including, without limitation, bacteriophage scaffold, virus scaffold, chemical based delivery vehicle (e.g., cyclodextrin, calcium phosphate, cationic polymers, cationic liposomes), protein-based or peptide-based delivery vehicle, lipid-based delivery vehicle, nanoparticle-based delivery vehicles, non-chemical-based delivery vehicles (e.g., transformation, electroporation, sonoporation, optical transfection), particle-based delivery vehicles (e.g., gene gun, magnetofection, impalefection, particle bombardment, cell-penetrating peptides) or donor bacteria (conjugation).
  • chemical based delivery vehicle e.g., cyclodextrin, calcium phosphate, cationic polymers, cationic liposomes
  • protein-based or peptide-based delivery vehicle e.g., lipid-based delivery vehicle, nanoparticle-based delivery vehicles, non-chemical-based delivery vehicles (e.g., transformation,
  • the delivery vehicle can refer to a bacteriophage derived scaffold and can be obtained from a natural, evolved or engineered capsid.
  • the delivery vehicle is the payload as bacteria are naturally competent to take up a payload from the environment on their own.
  • the term “payload” refers to any one or more nucleic acid sequence and/or amino acid sequence, or a combination of both (such as, without limitation, peptide nucleic acid or peptide-oligonucleotide conjugate) transferred into a bacterium with a delivery vehicle.
  • the term “payload” may also refer to a plasmid, a vector or a cargo.
  • the payload can be a phagemid or phasmid obtained from natural, evolved or engineered bacteriophage genome.
  • the payload can also be composed only in part of phagemid or phasmid obtained from natural, evolved or engineered bacteriophage genome.
  • nucleic acid refers to a sequence of at least two nucleotides covalently linked together which can be single-stranded or double-stranded or contains portion of both single-stranded and double-stranded sequence.
  • Nucleic acids of the present invention can be naturally occurring, recombinant or synthetic.
  • the nucleic acid can be in the form of a circular sequence or a linear sequence or a combination of both forms.
  • the nucleic acid can be DNA, both genomic or cDNA, or RNA or a combination of both.
  • the nucleic acid may contain any combination of deoxyribonucleotides and ribonucleotides, and any combination of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xathanine, hypoxathanine, isocytosine, 5-hydroxymethylcytosine and isoguanine.
  • bases including uracil, adenine, thymine, cytosine, guanine, inosine, xathanine, hypoxathanine, isocytosine, 5-hydroxymethylcytosine and isoguanine.
  • modified bases that can be used in the present invention are detailed in Chemical Reviews 2016, 116 (20) 12655-12687.
  • nucleic acid also encompasses any nucleic acid analogs which may contain other backbones comprising, without limitation, phosphoramide, phosphorothioate, phosphorodithioate, O-methylphophoroamidite linkage and/or deoxyribonucleotides and ribonucleotides nucleic acids. Any combination of the above features of a nucleic acid is also encompassed by the present invention.
  • Origins of replication known in the art have been identified from species-specific plasmid DNAs (e.g. CoIE1, R1, pT181, pSC101, pMB1, R6K, RK2, p15a and the like), from bacterial virus (e.g. ⁇ X174, M13, F1 and P4) and from bacterial chromosomal origins of replication (e.g. oriC).
  • the phagemid according to the disclosure comprises a bacterial origin of replication that is functional in the targeted bacteria.
  • the plasmid according to the disclosure does not comprise any functional bacterial origin of replication or contain an origin of replication that is inactive in the targeted bacteria. Thus, the plasmid of the disclosure cannot replicate by itself once it has been introduced into a bacterium by the bacterial virus particle.
  • the origin of replication on the plasmid to be packaged is inactive in the targeted bacteria, meaning that this origin of replication is not functional in the bacteria targeted by the bacterial virus particles, thus preventing unwanted plasmid replication.
  • the plasmid comprises a bacterial origin of replication that is functional in the bacteria used for the production of the bacterial virus particles.
  • Plasmid replication depends on host enzymes and on plasmid-controlled cis and trans determinants. For example, some plasmids have determinants that are recognized in almost all gram-negative bacteria and act correctly in each host during replication initiation and regulation. Other plasmids possess this ability only in some bacteria (Kues, U and Stahl, U 1989 Microbiol Rev 53:491-516).
  • Plasmids are replicated by three general mechanisms, namely theta type, strand displacement, and rolling circle (reviewed by Del Solar et al. 1998 Microhio and Molec Biol. Rev 62:434-464) that start at the origin of replication. These replication origins contain sites that are required for interactions of plasmid and/or host encoded proteins.
  • Origins of replication used on the plasmid of the disclosure may be of moderate copy number, such as colEl ori from pBR322 (15-20 copies per cell) or the R6K plasmid (15-20 copies per cell) or may be high copy number, e.g. pUC oris (500-700 copies per cell), pGEM oris (300-400 copies per cell), pTZ oris (>1000 copies per cell) or pBluescript oris (300-500 copies per cell).
  • moderate copy number such as colEl ori from pBR322 (15-20 copies per cell) or the R6K plasmid (15-20 copies per cell) or may be high copy number, e.g. pUC oris (500-700 copies per cell), pGEM oris (300-400 copies per cell), pTZ oris (>1000 copies per cell) or pBluescript oris (300-500 copies per cell).
  • the bacterial origin of replication is selected in the group consisting of ColE1, pMB1 and variants (pBR322, pET, pUC, etc), p15a, ColA, ColE2, pOSAK, pSC101, R6K, IncW (pSa etc), IncFII, pT181, P1, F IncP, IncC, IncJ, IncN, IncP1, IncP4, IncQ, IncH11, RSF1010, CloDF13, NTP16, R1, f5, pPS10, pC194, pE194, BBR1, pBC1, pEP2, pWVO1, pLF1311, pAP1, pWKS1, pLS1, pLS11, pUB6060, pJD4, 0E01, pSN22, pAMbetal, pIP501, pIP407, ZM6100(Sa), pCU1, RA3, pMOL98, RK2/RP4/RP1/R68,
  • the bacterial origin of replication is a E. coli origin of replication selected in the group consisting of ColE1, pMB1 and variants (pBR322, pET, pUC, etc), p15a, ColA, ColE2, pOSAK, pSC101, R6K, IncW (pSa etc), IncFII, pT181, P1, F IncP, IncC, IncJ, IncN, IncP1, IncP4, IncQ, IncH11, RSF1010, CloDF13, NTP16, R1, f5 and pPS10.
  • E. coli origin of replication selected in the group consisting of ColE1, pMB1 and variants (pBR322, pET, pUC, etc), p15a, ColA, ColE2, pOSAK, pSC101, R6K, IncW (pSa etc), IncFII, pT181, P1, F IncP, IncC, IncJ, IncN, IncP1, IncP4, IncQ, IncH11, RSF
  • the bacterial origin of replication is selected in the group consisting of pC194, pE194, BBR1, pBC1, pEP2, pWVO1, pLF1311, pAP1, pWKS1, pLS1, pLS11, pUB6060, pJD4, pIJ101, pSN22, pAMbetal, pIP501, pIP407, ZM6100(Sa), pCU1, RA3, pMOL98, RK2/RP4/RP1/R68, pB10, R300B, pRO1614, pRO1600, pECB2, pCM1, pFA3, RepFIA, RepFIB, RepFIC, pYVE439-80, R387, phasyl, RA1, TF-FC2, pMV158 and pUB113.
  • the bacterial origin of replication is ColE1.
  • the delivered nucleic acid sequence according to the disclosure may comprise a phage replication origin which can initiate, with complementation of a complete phage genome, the replication of the delivered nucleic acid sequence for later encapsulation into the different capsids.
  • a phage origin of replication comprised in the delivered nucleic acid sequence of the disclosure can be any origin of replication found in a phage.
  • the phage origin of replication can be the wild-type or non-wildtype sequence of the M13, f1, ⁇ X174, P4, lambda, P2, lambda-like, HK022, mEP237, HK97, HK629, HK630, mEP043, mEP213, mEP234, mEP390, mEP460, mEPx1, mEPx2, phi80, mEP234, T2, T4, T5, T7, RB49, phiX174, R17, PRD1 P1-like, P2-like, P22, P22-like, N15 and N15-like bacteriophages.
  • the phage origin of replication is selected in the group consisting of phage origins of replication of M13, f1, ⁇ X174, P4, and lambda.
  • the phage origin of replication is the lambda or P4 origin of replication.
  • the delivered nucleic acid of interest comprises a nucleic acid sequence under the control of a promoter.
  • the nucleic acid of interest is selected from the group consisting of a Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme such as a nuclease or a kinase, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor, a membrane protein, a structural protein, a secreted protein, a gene expressing resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any of their combination.
  • the nucleic acid payload encodes a therapeutic protein. In another embodiment, the nucleic acid payload encodes an anti-sense nucleic acid molecule. In some embodiment, the nucleic acid payload encodes 2 nucleic acids of interest, one being a nuclease gene, for instance a Cas nuclease gene, and one being any other nucleic acid of interest.
  • the sequence of interest is a programmable nuclease circuit to be delivered to the targeted bacteria.
  • This programmable nuclease circuit is able to mediate in vivo sequence-specific elimination of bacteria that contain a target gene of interest (e.g. a gene that is harmful to humans).
  • Some embodiments of the present disclosure relate to engineered variants of the Type II CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated) system of Streptococcus pyogenes .
  • programmable nucleases that can be used include other CRISPR-Cas systems, engineered TALEN (Transcription Activator-Like Effector Nuclease) variants, engineered zinc finger nuclease (ZFN) variants, natural, evolved or engineered meganuclease or recombinase variants, and any combination or hybrids of programmable nucleases.
  • the engineered autonomously distributed nuclease circuits provided herein may be used to selectively cleave DNA encoding a gene of interest such as, for example, a toxin gene, a virulence factor gene, an antibiotic resistance gene, a remodeling gene or a modulatory gene (cf. WO2014124226).
  • sequences of interest can be added to the delivered nucleic acid sequence so as to be delivered to targeted bacteria.
  • sequence of interest added to the delivered nucleic acid sequence leads to cell death of the targeted bacteria.
  • the nucleic acid sequence of interest added to the plasmid may encode holins or toxins.
  • sequence of interest circuit added to the delivered nucleic acid sequence does not lead to bacteria death.
  • the sequence of interest may encode reporter genes leading to a luminescence or fluorescence signal.
  • the sequence of interest may comprise proteins and enzymes achieving a useful function such as modifying the metabolism of the bacteria or the composition of its environment.
  • the nucleic sequence of interest is selected in the group consisting of Cas9, a single guide RNA (sgRNA), a CRISPR locus, a gene expressing an enzyme such as a nuclease or a kinase, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor, a membrane protein, a structural protein, a secreted protein, resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor and a gene expressing a virulence protein or a virulence factor.
  • sgRNA single guide RNA
  • CRISPR locus a gene expressing an enzyme such as a nuclease or a kinase, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor, a membrane protein, a structural protein,
  • the delivered nucleic acid sequence according to the disclosure comprises a nucleic acid sequence of interest that encodes a bacteriocin, which can be a proteinaceous toxin produced by bacteria to kill or inhibit growth of other bacteria.
  • Bacteriocins are categorized in several ways, including producing strain, common resistance mechanisms, and mechanism of killing. Such bacteriocin had been described from gram negative bacteria (e.g. microcins, colicin-like bacteriocins and tailocins) and from gram positive bacteria (e.g. Class I, Class II, Class III or Class IV bacteriocins).
  • the delivered nucleic acid sequence according to the disclosure further comprises a sequence of interest encoding a toxin selected in the group consisting of microcins, colicin-like bacteriocins, tailocins, Class I, Class II, Class III and Class IV bacteriocins.
  • the corresponding immunity polypeptide i.e. anti-toxin
  • the corresponding immunity polypeptide may be used to protect bacterial cells (Cotter et al., Nature Reviews Microbiology 11: 95, 2013, which is hereby incorporated by reference in its entirety) for delivered nucleic acid sequence production and encapsidation purpose but is absent in the pharmaceutical composition and in the targeted bacteria in which the delivered nucleic acid sequence of the disclosure is delivered.
  • the CRISPR system is included in the delivered nucleic acid sequence.
  • the CRISPR system contains two distinct elements, i.e. i) an endonuclease, in this case the CRISPR associated nuclease (Cas or “CRISPR associated protein”) and ii) a guide RNA.
  • the guide RNA is in the form of a chimeric RNA which consists of the combination of a CRISPR (RNAcr) bacterial RNA and a RNAtracr (trans-activating RNA CRISPR) (Jinek et al., Science 2012).
  • the guide RNA combines the targeting specificity of the RNAcr corresponding to the “spacing sequences” that serve as guides to the Cas proteins, and the conformational properties of the RNAtracr in a single transcript.
  • the target genomic sequence can be permanently modified or interrupted. The modification is advantageously guided by a repair matrix.
  • the CRISPR system includes two main classes depending on the nuclease mechanism of action. Class 1 is made of multi-subunit effector complexes and includes type I, III and IV.
  • Class 2 is made of single-unit effector modules, like Cas9 nuclease, and includes type II (II-A,II-B,II-C,II-C variant), V (V-A,V-B,V-C,V-D,V-E,V-U1,V-U2,V-U3,V-U4,V-U5) and VI (VI-A,VI-B1,VI-B2,VI-C,VI-D)
  • the sequence of interest comprises a nucleic acid sequence encoding Cas protein.
  • CRISPR enzymes are available for use as a sequence of interest on the plasmid.
  • the CRISPR enzyme is a Type II CRISPR enzyme.
  • the CRISPR enzyme catalyzes DNA cleavage.
  • the CRISPR enzyme catalyzes RNA cleavage.
  • the CRISPR enzymes may be coupled to a sgRNA.
  • the sgRNA targets a gene selected in the group consisting of an antibiotic resistance gene, virulence protein or factor gene, toxin protein or factor gene, a bacterial receptor gene, a membrane protein gene, a structural protein gene, a secreted protein gene and a gene expressing resistance to a drug in general.
  • Non-limiting examples of Cas proteins as part of a multi-subunit effector or as a single-unit effector include Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cash, Cas7, Cas8, Cas9 (also known as Csn1 and Csx12), Cas10, Cas11 (SS), Cas12a (Cpf1), Cas12b (C2c1), Cas12c (C2c3), Cas12d (CasY), Cas12e (CasX), C2c4, C2c8, C2c5, C2c10, C2c9, Cas13a (C2c2), Cas13b (C2c6), Cas13c (C2c7), Cas13d, Csa5, Csc1, Csc2, Cse1, Cse2, Csy1, Csy2, Csy3, Csf1, Csf2, Csf3, Csf4, Csm2, Csm3, Csm4, Cs
  • the CRISPR enzyme is any Cas9 protein, for instance any naturally-occurring bacterial Cas9 as well as any variants, homologs or orthologs thereof.
  • Cas9 is meant a protein Cas9 (also called Csn1 or Csx12) or a functional protein, peptide or polypeptide fragment thereof, i.e. capable of interacting with the guide RNA(s) and of exerting the enzymatic activity (nuclease) which allows it to perform the double-strand cleavage of the DNA of the target genome.
  • Cas9 can thus denote a modified protein, for example truncated to remove domains of the protein that are not essential for the predefined functions of the protein, in particular the domains that are not necessary for interaction with the gRNA (s).
  • Cas9 the entire protein or a fragment thereof
  • the sequence encoding Cas9 can be obtained from any known Cas9 protein (Fonfara et al., Nucleic Acids Res 42 (4), 2014; Koonin et al., Nat Rev Microbiol 15(3), 2017).
  • Cas9 proteins useful in the present disclosure include, but are not limited to, Cas9 proteins of Streptococcus pyogenes (SpCas9), Streptococcus thermophiles (St1Cas9, St3Cas9), Streptococcus mutans, Staphylococcus aureus (SaCas9), Campylobacter jejuni (CjCas9), Francisella novicida (FnCas9) and Neisseria meningitides (NmCas9).
  • Cpf1 (Cas12a) (the entire protein or a fragment thereof) as used in the context of the disclosure can be obtained from any known Cpf1 (Cas12a) protein (Koonin et al., 2017).
  • Cpf1(Cas12a) proteins useful in the present disclosure include, but are not limited to, Cpf1(Cas12a) proteins of Acidaminococcus sp, Lachnospiraceae bacteriu and Francisella novicida.
  • Cas13a (the entire protein or a fragment thereof) can be obtained from any known Cas13a (C2c2) protein (Abudayyeh et al., 2017).
  • Cas13a (C2c2) proteins useful in the present disclosure include, but are not limited to, Cas13a (C2c2) proteins of Leptotrichia wadei (LwaCas13 a).
  • Cas13d (the entire protein or a fragment thereof) can be obtained from any known Cas13d protein (Yan et al., 2018).
  • Cas13d proteins useful in the present disclosure include, but are not limited to, Cas13d proteins of Eubacterium siraeum and Ruminococcus sp.
  • the nucleic sequence of interest is a CRISPR/Cas9 system for the reduction of gene expression or inactivation a gene selected in the group consisting of an antibiotic resistance gene, virulence factor or protein gene, toxin factor or protein gene, a gene expressing a bacterial receptor, a membrane protein, a structural protein, a secreted protein, and a gene expressing resistance to a drug in general.
  • the CRISPR system is used to target and inactivate a virulence factor.
  • a virulence factor can be any substance produced by a pathogen that alter host-pathogen interaction by increasing the degree of damage done to the host.
  • Virulence factors are used by pathogens in many ways, including, for example, in cell adhesion or colonization of a niche in the host, to evade the host's immune response, to facilitate entry to and egress from host cells, to obtain nutrition from the host, or to inhibit other physiological processes in the host.
  • Virulence factors can include enzymes, endotoxins, adhesion factors, motility factors, factors involved in complement evasion, and factors that promote biofilm formation.
  • such targeted virulence factor gene can be E.
  • coli virulence factor gene such as, without limitation, EHEC-HlyA, Stx1 (VT1), Stx2 (VT2), Stx2a (VT2a), Stx2b (VT2b), Stx2c (VT2c), Stx2d (VT2d), Stx2e (VT2e) and Stx2f (VT2f), Stx2h (VT2h), fimA, fimF, fimH, neuC, kpsE, sfa, foc, iroN, aer, iha, papC, papGI, papGII, papGIII, hlyC, cnfl, hra, sat, ireA, usp ompT, ibeA, malX, fyuA, irp2, traT, afaD, ipaH, eltB, estA, bfpA, eaeA, espA, aai
  • such targeted virulence factor gene can be Shigella dysenteriae virulence factor gene such as, without limitation, stx1 and stx2.
  • such targeted virulence factor gene can be Yersinia pestis virulence factor gene such as, without limitation, yscF (plasmid-borne (pCD1) T3SS external needle subunit).
  • yscF plasmid-borne (pCD1) T3SS external needle subunit
  • such targeted virulence factor gene can be Francisella tularensis virulence factor gene such as, without limitation, fs1A.
  • such targeted virulence factor gene can be Bacillus anthracis virulence factor gene such as, without limitation, pag (Anthrax toxin, cell-binding protective antigen).
  • such targeted virulence factor gene can be Vibrio cholera virulence factor gene such as, without limitation, ctxA and ctxB (cholera toxin), tcpA (toxin co-regulated pilus), and toxT (master virulence regulator).
  • Vibrio cholera virulence factor gene such as, without limitation, ctxA and ctxB (cholera toxin), tcpA (toxin co-regulated pilus), and toxT (master virulence regulator).
  • such targeted virulence factor gene can be Pseudomonas aeruginosa virulence factor genes such as, without limitation, pyoverdine (e.g., sigma factor pvdS, biosynthetic genes pvdL, pvdl, pvdJ, pvdH, pvdA, pvdF, pvdQ, pvdN, pvdM, pvdO, pvdP, transporter genes pvdE, pvdR, pvdT, opmQ), siderophore pyochelin (e.g., pchD, pchC, pchB, pchA, pchE, pchF and pchG, and toxins (e.g., exoU, exoS and exoT).
  • pyoverdine e.g., sigma factor pvdS, bio
  • such targeted virulence factor gene can be Klebsiella pneumoniae virulence factor genes such as, without limitation, fimA (adherence, type I fimbriae major subunit), and cps (capsular polysaccharide).
  • Klebsiella pneumoniae virulence factor genes such as, without limitation, fimA (adherence, type I fimbriae major subunit), and cps (capsular polysaccharide).
  • such targeted virulence factor gene can be Acinetobacter baumannii virulence factor genes such as, without limitation, ptk (capsule polymerization) and epsA (assembly).
  • such targeted virulence factor gene can be Salmonella enterica Typhi virulence factor genes such as, without limitation, MIA (invasion, SPI-1 regulator), ssrB (SPI-2 regulator), and those associated with bile tolerance, including efflux pump genes acrA, acrB and tolC.
  • such targeted virulence factor gene can be Fusobacterium nucleatum virulence factor genes such as, without limitation, FadA and TIGIT.
  • such targeted virulence factor gene can be Bacteroides fragilis virulence factor genes such as, without limitation, bft.
  • the CRISPR/Cas9 system is used to target and inactivate an antibiotic resistance gene such as, without limitation, GyrB, ParE, ParY, AAC(1), AAC(2′), AAC(3), AAC(6′), ANT(2′′), ANT(3′′), ANT(4′), ANT(6), ANT(9), APH(2′′), APH(3′′), APH(3′), APH(4), APH(6), APH(7′′), APH(9), ArmA, RmtA, RmtB, RmtC, Sgm, AER, BLA1, CTX-M, KPC, SHV, TEM, BlaB, CcrA, IMP, NDM, VIM, ACT, AmpC, CMY, LAT, PDC, OXA ⁇ -lactamase, mecA, Omp36, OmpF, PIB, bla (blaI, blaR1) and mec (mecl, mecR1) operons,
  • the CRISPR/Cas9 system is used to target and inactivate a bacterial toxin gene.
  • Bacterial toxin can be classified as either exotoxins or endotoxins. Exotoxins are generated and actively secreted; endotoxins remain part of the bacteria. The response to a bacterial toxin can involve severe inflammation and can lead to sepsis.
  • Such toxin can be for example Botulinum neurotoxin, Tetanus toxin, Staphylococus toxins, Diphteria toxin, Anthrax toxin, Alpha toxin, Pertussis toxin, Shiga toxin, Heat-stable enterotoxin ( E. coli ST), colibactin, BFT ( B. fragilis toxin) or any toxin described in Henkel et al., (Toxins from Bacteria in EXS. 2010; 100: 1-29).
  • the bacteria targeted by bacterial delivery vehicles disclosed herein can be any bacteria present in a mammal organism.
  • the bacteria are targeted through interaction of the chimeric RBPs expressed by the delivery vehicles with the bacterial cell. It can be any commensal, symbiotic or pathogenic bacteria of the microbiota or microbiome.
  • a microbiome may comprise of a variety of endogenous bacterial species, any of which may be targeted in accordance with the present disclosure.
  • the genus and/or species of targeted endogenous bacterial cells may depend on the type of bacteriophages being used for preparing the bacterial delivery vehicles. For example, some bacteriophages exhibit tropism for, or preferentially target, specific host species of bacteria. Other bacteriophages do not exhibit such tropism and may be used to target a number of different genus and/or species of endogenous bacterial cells.
  • bacterial cells include, without limitation, cells from bacteria of the genus Yersinia spp., Escherichia spp., Klebsiella spp., Acinetobacter spp., Bordetella spp., Neisseria spp., Aeromonas spp., Franciesella spp., Corynebacterium spp., Citrobacter spp., Chlamydia spp., Hemophilus spp., Brucella spp., Mycobacterium spp., Legionella spp., Rhodococcus spp., Pseudomonas spp., Helicobacter spp., Vibrio spp., Bacillus spp., Erysipelothrix spp., Salmonella spp., Streptomyces spp., Streptococcus spp., Staphylococcus spppp
  • bacterial delivery vehicles may target (e.g., specifically target) a bacterial cell from any one or more of the foregoing genus of bacteria to specifically deliver the payload of interest according to the disclosure.
  • the targeted bacteria can be selected from the group consisting of Yersinia spp., Escherichia spp., Klebsiella spp., Acinetobacter spp., Pseudomonas spp., Helicobacter spp., Vibrio spp, Salmonella spp., Streptococcus spp., Staphylococcus spp., Bacteroides spp., Clostridium spp., Shigella spp., Enterococcus spp., Enterobacter spp., Listeria spp., Cutibacterium spp., Propionibacterium spp., Fusobacterium spp., Porphyromonas spp. and Gardnerella spp.
  • bacterial cells of the present disclosure are anaerobic bacterial cells (e.g., cells that do not require oxygen for growth).
  • Anaerobic bacterial cells include facultative anaerobic cells such as but not limited to Escherichia coli, Shewanella oneidensis, Gardnerella vaginalis and Listeria .
  • Anaerobic bacterial cells also include obligate anaerobic cells such as, for example, Bacteroides, Clostridium, Cutibacterium, Propionibacterium, Fusobacterium and Porphyromona species.
  • anaerobic bacteria are most commonly found in the gastrointestinal tract.
  • the targeted bacteria are thus bacteria most commonly found in the gastrointestinal tract.
  • Bacteriophages used for preparing the bacterial virus particles, and then the bacterial virus particles may target (e.g., to specifically target) anaerobic bacterial cells according to their specific spectra known by the person skilled in the art to specifically deliver the plasmid.
  • the targeted bacterial cells are, without limitation, Bacteroides thetaiotaomicron, Bacteroides fragilis, Bacteroides distasonis, Bacteroides vulgatus, Clostridium leptum, Clostridium coccoides, Staphylococcus aureus, Bacillus subtilis, Clostridium butyricum, Brevibacterium lactofermentum, Streptococcus agalactiae, Lactococcus lactis, Leuconostoc lactis, Actinobacillus actinobycetemcomitans, cyanobacteria, Escherichia coli, Helicobacter pylori, Selnomonas ruminatium, Shigella sonnei, Zymomonas mobilis, Mycoplasma mycoides, Treponema denticola, Bacillus thuringiensis, Staphilococcus lugdunensis, Leuconost
  • the targeted bacteria are Escherichia coli.
  • bacteriophages used for preparing the bacterial delivery vehicles, and then the bacterial delivery vehicles may target (e.g., specifically target) a bacterial cell from any one or more of the foregoing genus and/or species of bacteria to specifically deliver the plasmid.
  • the targeted bacteria are pathogenic bacteria.
  • the targeted bacteria can be virulent bacteria.
  • the targeted bacteria can be antibacterial resistance bacteria, preferably selected from the group consisting of extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli , ESBL Klebsiella pneumoniae , vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant (MDR) Acinetobacter baumannii , MDR Enterobacter spp., and a combination thereof.
  • the targeted bacteria can be selected from the group consisting of extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli strains.
  • the targeted bacterium can be a bacterium of the microbiome of a given species, preferably a bacterium of the human microbiota.
  • the present disclosure is directed to bacterial delivery vehicle containing the payload as described herein.
  • the bacterial delivery vehicles are prepared from bacterial virus.
  • the bacterial delivery vehicles are chosen in order to be able to introduce the payload into the targeted bacteria.
  • Bacterial viruses from which the bacterial delivery vehicles having chimeric receptor binding proteins may be derived, are preferably bacteriophages.
  • the bacteriophage is selected from the Order Caudovirales consisting of, based on the taxonomy of Krupovic et al, Arch Virol, 2015:
  • Bacteriophages may be selected from the family Myoviridae (such as, without limitation, genus Cp220virus, Cplvirus, Ea214virus, Felixolvirus, Mooglevirus, Suspvirus, Hp1virus, P2virus, Kayvirus, P100virus, Etavirus, Spolvirus, Tsarbombavirus, Twortvirus, Cc31virus, Jd18virus, Js98virus, Kp15virus, Moonvirus, Rb49virus, Rb69virus, S16virus, Schizot4virus, Sp18virus, T4virus, Cr3virus, Selvirus, V5virus, Abouovirus, Agatevirus, Agrican357virus, Ap22virus, Arvlvirus, B4virus, Bastillevirus, Bc431virus, Bcep78virus, Bcepmuvirus, Biquartavirus, Bxz1virus, Cd119virus, Cp51virus, Cvm10virus, Eah2virus, Elvirus, Hapunavirus, Jimmervirus, Kpp
  • Bacteriophages may be selected from the family Podoviridae (such as, without limitation, genus Fri1virus, Kp32virus, Kp34virus, Phikmvvirus, Pradovirus, Sp6virus, T7virus, Cp1virus, P68virus, Phi29virus, Nona33virus, Pocjvirus, Tl2011virus, Bcep22virus, Bpplvirus, Cba41virus, Dfl12virus, Ea92virus, Epsilon15virus, F116virus, G7cvirus, Jwalphavirus, Kflvirus, Kpp25virus, Lit1virus, Luz24virus, Luz7virus, N4virus, Nonanavirus, P22virus, Pagevirus, Phieco32virus, Prtbvirus, Sp58virus, Una961virus and Vp5virus)
  • Podoviridae such as, without limitation, genus Fri1virus, Kp32virus, Kp34virus, Phikmvvirus, Pradovirus, Sp6virus, T7virus, C
  • Bacteriophages may be selected from the family Ackermannviridae (such as, without limitation, genus Ag3virus, Limestonevirus, Cba120virus and Vi1virus)
  • the bacteriophage is not part of the order Caudovirales but from families with unassigned order such as, without limitation, family Tectiviridae (such as genus Alphatectivirus , Betatectivirus), family Corticoviridae (such as genus Corticovirus ), family Inoviridae (such as genus Fibrovirus , Habenivirus, Inovirus, Lineavirus, Plectrovirus, Saetivirus, Vespertiliovirus), family Cystoviridae(such as genus Cystovirus ), family Leviviridae(such as genus Allolevivirus , Levivirus), family Microviridae (such as genus Alpha3microvirus, G4microvirus, Phix174microvirus, Bdellomicrovirus, Chlamydiamicrovirus, Spiromicrovirus) and family Plasmaviridae (such as genus Plasmavirus ).
  • family Tectiviridae such as genus Alphatectivirus
  • the bacteriophage is targeting Archea not part of the Order Caudovirales but from families with Unassigned order such as, without limitation, Ampullaviridae, FuselloViridae, Globuloviridae, Guttaviridae, Lipothrixviridae, Pleolipoviridae, Rudiviridae, Salterprovirus and Bicaudaviridae.
  • chimeric RBPs and the bacterial delivery vehicles disclosed herein may be engineered, as non-limiting examples, from the following phages.
  • Synonyms and spelling variants are indicated in parentheses. Homonyms are repeated as often as they occur (e.g., D, D, d). Unnamed phages are indicated by “NN” beside their genus and their numbers are given in parentheses.
  • Bacteria of the genus Actinomyces can be infected by the following phages: Av-I, Av-2, Av-3, BF307, CT1, CT2, CT3, CT4, CT6, CT7, CT8 and 1281.
  • Bacteria of the genus Bacillus can be infected by the following phages: A, aizl, Al—K—I, B, BCJA1, BC1, BC2, BLL1, BL1, BP142, BSL1, BSL2, BS1, BS3, BS8, BS15, BS18, BS22, BS26, BS28, BS31, BS104, BS105, BS106, BTB, B1715V1, C, CK-I, Coll, Corl, CP-53, CS-I, CSi, D, D, D, D5, entl, FP8, FP9, FSi, FS2, FS3, FS5, FS8, FS9, G, GH8, GT8, GV-I, GV-2, GT-4, g3, g12, g13, g14, g16, g17, g21, g23, g24, g29, H2, kenl, KK-88, Kuml,
  • Bacillus -specific phages are defective: DLP10716, DLP-11946, DPB5, DPB12, DPB21, DPB22, DPB23, GA-2, M, No. IM, PBLB, PBSH, PBSV, PBSW, PBSX, PBSY, PBSZ, phi, SPa, type 1 and ⁇ .
  • Bacteria of the genus Bacteriodes can be infected by the following phages: ad I2, Baf-44, Baf-48B, Baf-64, Bf-I, Bf-52, B40-8, F1, ⁇ 1, ⁇ A1, ⁇ BrO1, ⁇ BrO2, 11, 67.1, 67.3, 68.1, mt-Bacteroides (3), Bf42, Bf71, HN-Bdellovibrio (1) and BF-41.
  • Bacteria of the genus Bordetella can be infected by the following phages: 134 and NN- Bordetella (3).
  • Bacteria of the genus Borrellia can be infected by the following phages: NN-Borrelia (1) and NN-Borrelia (2).
  • Bacteria of the genus Burkholderia can be infected by the following phages: CP75, NN- Burkholderia (1) and 42.
  • Bacteria of the genus Chlamydia can be infected by the following phage: Chpl.
  • Bacteria of the genus Enterococcus are infected by the following phage: DF78, F1, F2, 1, 2, 4, 14, 41, 867, Dl, SB24, 2BV, 182, 225, C2, C2F, E3, E62, DS96, H24, M35, P3, P9, SB1O1, S2, 2BII, 5, 182a, 705, 873, 881, 940, 1051, 1057, 21096C, NN- Enterococcus (1), PE1, F1, F3, F4, VD13, 1, 200, 235 and 341.
  • Bacteria of the genus Erysipelothrix can be infected by the following phage: NN-Eiysipelothrix (1).
  • Bacteria of the genus Fusobacterium are infected by the following phage: NN-Fusobacterium (2), fv83-554/3, fv88-531/2, 227, fv2377, fv2527 and fv8501.
  • Bacteria of the genus Haemophilus are infected by the following phage: HP1, S2 and N3.
  • Bacteria of the genus Helicobacter are infected by the following phage: HP1 and ⁇ circumflex over ( ) ⁇ circumflex over ( ) ⁇ - Helicobacter (1).
  • Bacteria of the genus Lepitospira are infected by the following phage: LEl, LE3, LE4 and ⁇ NN-Leptospira (1).
  • Bacteria of the genus Morganella are infected by the following phage: 47.
  • Bacteria of the genus Neisseria are infected by the following phage: Group I, group II and NPl.
  • Bacteria of the genus Nocardia are infected by the following phage: MNP8, NJ-L, NS-8, N5 and TtiN-Nocardia.
  • Bacteria of the genus Proteus are infected by the following phage: Pm5, 13vir, 2/44, 4/545, 6/1004, 13/807, 20/826, 57, 67b, 78, 107/69, 121, 9/0, 22/608, 30/680, PmI, Pm3, Pm4, Pm6, Pm7, Pm9, PmIO, PmI l, Pv2, ⁇ l, ⁇ m, 7/549, 9B/2, 10A/31, 12/55, 14, 15, 16/789, 17/971, 19A/653, 23/532, 25/909, 26/219, 27/953, 32A/909, 33/971, 34/13, 65, 5006M, 7480b, VI, 13/3a, Clichy 12, ⁇ 2600, ⁇ 7, 1/1004, 5/742, 9, 12, 14, 22, 24/860, 2600/D52, Pm8 and 24/2514.
  • Bacteria of the genus Providencia are infected by the following phage: PL25, PL26, PL37, 9211/9295, 9213/921 Ib, 9248, 7/R49, 7476/322, 7478/325, 7479, 7480, 9000/9402 and 9213/921 Ia.
  • Bacteria of the genus Rickettsia are infected by the following phage: NN-Rickettsia.
  • Bacteria of the genus Serratia are infected by the following phage: A2P, PS20, SMB3, SMP, SMP5, SM2, V40, V56, ic, ⁇ CP-3, ⁇ CP-6, 3M, 10/la, 20A, 34CC, 34H, 38T, 345G, 345P, 501B, SMB2, SMP2, BC, BT, CW2, CW3, CW4, CW5, Lt232, L2232, L34, L.228, SLP, SMPA, V.43, ⁇ , ⁇ CWl, ⁇ CP6-1, ⁇ CP6-2, ⁇ CP6-5, 3T, 5, 8, 9F, 10/1, 2OE, 32/6, 34B, 34CT, 34P, 37, 41, 56, 56D, 56P, 6OP, 61/6, 74/6, 76/4, 101/8900, 226, 227, 228, 229F, 286, 289, 290F, 512, 764a, 2847/10, 28
  • Bacteria of the genus Treponema are infected by the following phage: NN- Treponema (1).
  • Bacteria of the genus Yersinia are infected by the following phage: H, H-I, H-2, H-3, H-4, Lucas 110, Lucas 303, Lucas 404, YerA3, YerA7, YerA20, YerA41, 3/M64-76, 5/G394-76, 6/C753-76, 8/C239-76, 9/F18167, 1701, 1710, PST, 1/F2852-76, D+Herelle, EV, H, Kotljarova, PTB, R, Y, YerA41, ⁇ YerO3-12, 3, 4/C1324-76, 7/F783-76, 903, 1/M6176 and Yer2AT.
  • the bacteriophage is selected in the group consisting of Salmonella virus SKML39, Shigella virus AG3, Dickeya virus Limestone, Dickeya virus RC2014, Escherichia virus CBA120, Escherichia virus Phaxl, Salmonella virus 38, Salmonella virus Det7, Salmonella virus GG32, Salmonella virus PM10, Salmonella virus SFP10, Salmonella virus SH19 , Salmonella virus SJ3, Escherichia virus ECML4, Salmonella virus Marshall, Salmonella virus Maynard, Salmonella virus SJ2, Salmonella virus STML131, Salmonella virus ViI, Erwinia virus Ea2809, Klebsiella virus 0507KN21, Serratia virus IME250, Serratia virus MAM1, Campylobacter virus CP21, Campylobacter virus CP220, Campylobacter virus CPt10, Campylobacter virus IBB35, Campylobacter virus CP81, Campylobacter virus CP
  • the bacterial virus particles target E. coli and includes the capsid of a bacteriophage selected in the group consisting of BW73, B278, D6, D108, E, El, E24, E41, FI-2, FI-4, FI-5, HI8A, Ffl8B, i, MM, Mu, 025, PhI-5, Pk, PSP3, Pl, PlD, P2, P4, Sl, W ⁇ , ⁇ K13, ⁇ l, ⁇ 2, ⁇ 7, ⁇ 92, 7 A, 8 ⁇ , 9 ⁇ , 18, 28-1, 186, 299, HH- Escherichia (2), AB48, CM, C4, C16, DD-VI, E4, E7, E28, FE, FI3, H, Hl, H3, H8, K3, M, N, ND-2, ND-3, ND4, ND-5, ND6, ND-7, Ox-I, Ox-2, Ox-3, Ox-4, Ox-5, Ox-6, PhI-I
  • Prebiotics include, but are not limited to, amino acids, biotin, fructo-oligosaccharide, galacto-oligosaccharides, hemicelluloses (e.g., arabinoxylan, xylan, xyloglucan, and glucomannan), inulin, chitin, lactulose, mannan oligosaccharides, oligofructose-enriched inulin, gums (e.g., guar gum, gum arabic and carregenaan), oligofructose, oligodextrose, tagatose, resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide, pectins (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fibers (e.g., soy fiber, sugarbeet fiber,
  • Probiotics include, but are not limited to lactobacilli, bifidobacteria, streptococci, enterococci, propionibacteria, saccaromycetes, lactobacilli, bifidobacteria, or proteobacteria.
  • the antibiotic can be selected from the group consisting in penicillins such as penicillin G, penicillin K, penicillin N, penicillin O, penicillin V, methicillin, benzylpenicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, ampicillin, amoxicillin, pivampicillin, hetacillin, bacampicillin, metampicillin, talampicillin, epicillin, carbenicillin, ticarcillin, temocillin, mezlocillin, and piperacillin; cephalosporins such as cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cefalotin, cefapirin, cefatrizine, cefazaflur, cefazedone, cefazolin, cefradine, cefroxadine, ceftezole, cefaclor, cefonicid
  • the present invention provides pharmaceutical or veterinary compositions comprising one or more of the bacterial delivery vehicles disclosed herein and a pharmaceutically-acceptable carrier.
  • the bacterial delivery vehicles may be formulated as a pharmaceutical preparation or compositions comprising at least one bacterial delivery vehicles and at least one pharmaceutically acceptable carrier, diluent or excipient, and optionally one or more further pharmaceutically active compounds.
  • Such a formulation may be in a form suitable for oral administration, for parenteral administration (such as by intravenous, intramuscular or subcutaneous injection or intravenous infusion), for topical administration, for administration by inhalation, by a skin patch, by an implant, by a suppository, etc.
  • Such administration forms may be solid, semi-solid or liquid, depending on the manner and route of administration.
  • formulations for oral administration may be provided with an enteric coating that will allow the synthetic bacterial delivery vehicles in the formulation to resist the gastric environment and pass into the intestines.
  • synthetic bacterial delivery vehicle formulations for oral administration may be suitably formulated for delivery into any desired part of the gastrointestinal tract.
  • suitable suppositories may be used for delivery into the gastrointestinal tract.
  • Various pharmaceutically acceptable carriers, diluents and excipients useful in bacterial delivery vehicle compositions are known to the skilled person.
  • kits for treating a bacterial infection using the synthetic bacterial delivery vehicles disclosed herein include administering the synthetic bacterial delivery vehicles or compositions disclosed herein to a subject having a bacterial infection in need of treatment.
  • the subject is a mammal. In some embodiments, the subject is a human.
  • the pharmaceutical or veterinary composition according to the disclosure may further comprise a pharmaceutically acceptable vehicle.
  • a solid pharmaceutically acceptable vehicle may include one or more substances which may also act as flavouring agents, lubricants, solubilisers, suspending agents, dyes, fillers, glidants, compression aids, inert binders, sweeteners, preservatives, dyes, coatings, or tablet-disintegrating agents.
  • Suitable solid vehicles include, for example calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.
  • the pharmaceutical or veterinary composition may be prepared as a sterile solid composition that may be suspended at the time of administration using sterile water, saline, or other appropriate sterile injectable medium.
  • the pharmaceutical or veterinary compositions of the disclosure may be administered orally in the form of a sterile solution or suspension containing other solutes or suspending agents (for example, enough saline or glucose to make the solution isotonic), bile salts, acacia, gelatin, sorbitan monoleate, polysorbate 8o (oleate esters of sorbitol and its anhydrides copolymerized with ethylene oxide) and the like.
  • the particles according to the disclosure can also be administered orally either in liquid or solid composition form.
  • compositions suitable for oral administration include solid forms, such as pills, capsules, granules, tablets, and powders, and liquid forms, such as solutions, syrups, elixirs, and suspensions.
  • forms useful for enteral administration include sterile solutions, emulsions, and suspensions.
  • the bacterial delivery vehicles according to the disclosure may be dissolved or suspended in a pharmaceutically acceptable liquid vehicle such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats.
  • a pharmaceutically acceptable liquid vehicle such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats.
  • the liquid vehicle can contain other suitable pharmaceutical additives such as solubilisers, emulsifiers, buffers, preservatives, sweeteners, flavouring agents, suspending agents, thickening agents, colours, viscosity regulators, stabilizers or osmo-regulators.
  • suitable examples of liquid vehicles for oral and enteral administration include water (partially containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g.
  • the vehicle can also be an oily ester such as ethyl oleate and isopropyl myristate.
  • Sterile liquid vehicles are useful in sterile liquid form compositions for enteral administration.
  • the liquid vehicle for pressurized compositions can be a halogenated hydrocarbon or other pharmaceutically acceptable propellant.
  • the pharmaceutical or veterinary composition can be formulated into ointment, cream or gel form and appropriate penetrants or detergents could be used to facilitate permeation, such as dimethyl sulfoxide, dimethyl acetamide and dimethylformamide.
  • nasal sprays for transmucosal administration, nasal sprays, rectal or vaginal suppositories can be used.
  • the active compounds can be incorporated into any of the known suppository bases by methods known in the art. Examples of such bases include cocoa butter, polyethylene glycols (carbowaxes), polyethylene sorbitan monostearate, and mixtures of these with other compatible materials to modify the melting point or dissolution rate.
  • the diseases or disorders caused by bacteria may be selected from the group consisting of abdominal cramps, acne vulgaris, acute epiglottitis, arthritis, bacteraemia, bloody diarrhea, botulism, Brucellosis, brain abscess, chancroid venereal disease, Chlamydia, Crohn's disease, conjunctivitis, cholecystitis, colorectal cancer, polyposis, dysbiosis, Lyme disease, diarrhea, diphtheria, duodenal ulcers, endocarditis, erysipelothricosis, enteric fever, fever, glomerulonephritis, gastroenteritis, gastric ulcers, Guillain-Barre syndrome tetanus, gonorrhoea, gingivitis, inflammatory bowel diseases, irritable bowel syndrome, leptospirosis, leprosy, listeriosis, tuberculosis, Lady Widermere syndrome, Legionaire's disease, meningitis, mu
  • the infection caused by bacteria may be selected from the group consisting of skin infections such as acne, intestinal infections such as esophagitis, gastritis, enteritis, colitis, sigmoiditis, rectitis, and peritonitis, urinary tract infections, vaginal infections, female upper genital tract infections such as salpingitis, endometritis, oophoritis, myometritis, parametritis and infection in the pelvic peritoneum, respiratory tract infections such as pneumonia, intra-amniotic infections, odontogenic infections, endodontic infections, fibrosis, meningitis, bloodstream infections, nosocomial infection such as catheter-related infections, hospital acquired pneumonia, post-partum infection, hospital acquired gastroenteritis, hospital acquired urinary tract infections, or a combination thereof.
  • the infection according to the disclosure is caused by a bacterium presenting an antibiotic resistance.
  • the infection is caused by a bacterium as listed above in the targeted bacteria.
  • the disclosure concerns a pharmaceutical or veterinary composition for use in the treatment of metabolic disorder including, for example, obesity and diabetes.
  • the disclosure concerns a pharmaceutical or veterinary composition for use in the treatment of pathologies involving bacteria of the human microbiome, such as inflammatory and auto-immune diseases, cancers, infections or brain disorders.
  • bacteria of the human microbiome such as inflammatory and auto-immune diseases, cancers, infections or brain disorders.
  • some bacteria of the microbiome without triggering any infection, can secrete molecules that will induce and/or enhance inflammatory or auto-immune diseases or cancer development.
  • the present disclosure relates also to modulating microbiome composition to improve the efficacy of immunotherapies based, for example, on CAR-T (Chimeric Antigen Receptor T) cells, TIL (Tumor Infiltrating Lymphocytes) and Tregs (Regulatory T cells) also known as suppressor T cells.
  • CAR-T Chimeric Antigen Receptor T
  • TIL Tumor Infiltrating Lymphocytes
  • Tregs Regulatory T cells
  • Modulation of the microbiome composition to improve the efficacy of immunotherapies may also include the use of immune checkpoint inhibitors well known in the art such as, without limitation, PD-1 (programmed cell death protein 1) inhibitor, PD-L1 (programmed death ligand 1) inhibitor and CTLA-4 (cytotoxic T lymphocyte associated protein 4).
  • immune checkpoint inhibitors well known in the art such as, without limitation, PD-1 (programmed cell death protein 1) inhibitor, PD-L1 (programmed death ligand 1) inhibitor and CTLA-4 (cytotoxic T lymphocyte associated protein 4).
  • Some bacteria of the microbiome can also secrete molecules that will affect the brain.
  • a further object of the disclosure is a method for controlling the microbiome of a subject, comprising administering an effective amount of the pharmaceutical composition as disclosed herein in said subject.
  • the disclosure also relates to a method for personalized treatment for an individual in need of treatment for a bacterial infection comprising: i) obtaining a biological sample from the individual and determining a group of bacterial DNA sequences from the sample; ii) based on the determining of the sequences, identifying one or more pathogenic bacterial strains or species that were in the sample; and iii) administering to the individual a pharmaceutical composition according to the disclosure capable of recognizing each pathogenic bacterial strain or species identified in the sample and to deliver the packaged plasmid.
  • the biological sample comprises pathological and non-pathological bacterial species, and subsequent to administering the pharmaceutical or veterinary composition according to the disclosure to the individual, the amount of pathogenic bacteria on or in the individual are reduced, but the amount of non-pathogenic bacteria is not reduced.
  • the disclosure concerns a pharmaceutical or veterinary composition according to the disclosure for use in order to improve the effectiveness of drugs.
  • some bacteria of the microbiome without being pathogenic by themselves, are known to be able to metabolize drugs and to modify them in ineffective or harmful molecules.
  • the disclosure concerns the in-situ bacterial production of any compound of interest, including therapeutic compound such as prophylactic and therapeutic vaccine for mammals.
  • the compound of interest can be produced inside the targeted bacteria, secreted from the targeted bacteria or expressed on the surface of the targeted bacteria.
  • an antigen is expressed on the surface of the targeted bacteria for prophylactic and/or therapeutic vaccination.
  • the present disclosure also relates to a non-therapeutic use of the bacterial delivery particles.
  • the non-therapeutic use can be a cosmetic use or a use for improving the well-being of a subject, in particular a subject who does not suffer from a disease.
  • the present disclosure also relates to a cosmetic composition or a non-therapeutic composition comprising the bacterial delivery particles if the disclosure.
  • a significative portion of a lambda receptor binding protein e.g. the stf protein
  • RBP lambda receptor binding protein
  • specific fusion positions in the lambda RBP have been identified which allow one to obtain a functional chimeric RBP.
  • the data demonstrate, in a non-limiting embodiment, that in the case of phagemids derived from bacteriophage lambda, modifying the side tail fiber protein results in an expanded host range.
  • the addition of chimeric stf proteins to lambdoid phagemids is demonstrated to be a very powerful approach to modify and increase their host range, and in some cases is more efficient than the modification of the gpJ gene.
  • modification of the side tail fiber protein to encode depolymerase activities can dramatically increase the delivery efficiency.
  • the addition of this enzymatic activity allows for 100% delivery efficiency while the wild-type lambda phagemid showed no entry at all.
  • the sequence of lambda stf (SEQ ID NO: 1) is: MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRY SMDVEYGQYSVILQVDGEPPSHAGTITVYEDSQPGTLNDFLCAMTEDDA RPEVLRRLELMVEEVARNASVVAQSTADAKKSAGDASASAAQVAALVTD ATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAAAAESSKNA AATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEA AKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASA AADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKR AEDIASAVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETN RKAPLDSPALTGTPTAPTALRGTNNTQIANTAFVLAAIADVIDASPDAL NTLNELAAA
  • the bold and underlined sequence represents the part of the protein that was introduced in the T4 phage [47].
  • Experiments were conducted to investigate if it was possible to exchange the C-terminus of the lambda stf with a tail fiber from a different phage to yield chimeric side tail fibers with an enzymatic activity against encapsulated E. coli .
  • the tail fiber from the K1F phage which has been studied in depth and its structure solved [19], [20] was chosen.
  • K1F encodes an enzyme with endosialidase activity, which is active against polymer of sialic acid secreted by K1-encapsulated E. coli .
  • K1+ strains are immune to T7 infection because the capsule forms a physical barrier that prevents attachment of the phage, but if purified K1F enzyme is added to the cells before infection, T7 is able to lyse them [21], confirming that the presence of bacterial capsules is a powerful mechanism to avoid recognition by bacteriophages.
  • K1+ strains are immune to T7 infection because the capsule forms a physical barrier that prevents attachment of the phage, but if purified K1F enzyme is added to the cells before infection, T7 is able to lyse them [21], confirming that the presence of bacterial capsules is a powerful mechanism to avoid recognition by bacteriophages.
  • K1F tail fiber (SEQ ID NO: 121) is: MSTITQFPSGNTQYRIEFDYLARTFVVVTLVNSSNPTLNRVLEVGRDYR FLNPTMIEMLVDQSGFDIVRIHRQTGTDLVVDFRNGSVLTASDLTTAEL QAIHIAEEGRDQTVDLAKEYADAAGSSAGNAKDSEDEARRIAESIRAAG LIGYMTRRSFEKGYNVTTWSEVLLWEEDGDYYRWDGTLPKNVPAGSTPE TSGGIGLGAWVSVGDAALRSQISNPEGAILYPELHRARWLDEKDARGW G AKGDGVTDDTAALTSALNDTPVGQKINGNGKTYKVTSLPDISRFINTRF VYERIPGQPLYYASEEFVQGELFKITDTPYYNAWPQDKAFVYENVIYAP YMGSDRHGVSRLHVSWVKSGDDGQTWSTPEWLTDLHPDYPTVNYHCMSM GVCRNRLFAMIETRTLAKN
  • the bold and underlined sequence represents the part of the protein that has been crystalized and has been shown to retain its endosialidase activity. Since there is no identity between the lambda stf protein and the K1F tail fiber, the insertion point was made based on conclusions extracted from different sources of information, including literature and crystal structures.
  • the stf gene was modified to include the K1F endosialidase at its C-terminus using a Cas9-mediated gene exchange protocol [22].
  • lambda-K1F phagemids were produced as in [23] and titrated against some K1+ strains, specifically E. coli UTI89 and S88. The results were striking; in these strains, there is no delivery if lambda wild-type stf is used, but the addition of the K1F variant gives 100% delivery ( FIG. 2 ).
  • side tail fibers can be found that have some degree of homology to lambda stf, although no crystal structure is available.
  • the insertion point was designed as the last stretch of amino acids with identity to lambda stf.
  • the predicted side tail fiber proteins are as follows:
  • the addition of a chimeric stf allows the lambda-based phagemid to show increased delivery efficiency in 25 out of 96 strains tested (more than 25% of the collection). In some cases, the increase is modest; in others, it allows for very good delivery efficiency in strains that had no or very low entry with wild-type lambda phagemids. It is also worth noting that AG22 belongs to the Siphovirus_family, like lambda, but SIEA11 is a P2-like phage. This highlights the significant observation that stf modules can be exchanged across bacteriophage genera.
  • Lambda stf (SEQ ID NO: 1) MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQST A DAKKS AGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAAAA ESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSETNASSS AGRAASSATAAENSARAAKTSETNARSSETAAER SASAAA DAKTAAAGSASTKATEAAGSAV SASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVV MDETNR KAPLDSPALTGTPTAPTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALG NDPDFATT
  • the lambda stf protein consists of 774 aminoacids.
  • the insertion points can be found closer to the N-terminus (amino acid 131, insertion point ADAKKS (SEQ ID NO: 249)) or closer to the C-terminus (amino acid 529, insertion point GAGENS (SEQ ID NO: 252)).
  • FIG. 5 depicts some selected examples for the insertion points ADAKKS (SEQ ID NO: 249), SASAAA (SEQ ID NO: 251) and MDETNR (SEQ ID NO: 250).
  • T4-like phages are a very diverse family of bacteriophages that share a common long tail fiber architecture: a proximal tail fiber that attaches to the phage particle and a distal tail fiber (DTF) that encodes host specificity linked by proteins acting as “hinge connectors” (Desplats and Krisch, 2003, Res. Microbiol. 154:259-267; Bartual et al. 2010, Proc. Natl. Acad. Sci. 107: 20287-20292). It is thought that the main host range determinants of the tail fiber reside in the distal part.
  • DTF distal tail fiber
  • T4-like phage which are known to be very broad, to any other phage or phagemid of interest.
  • the distal tail fiber (C-terminal domain of the T4-like long tail fiber) of several T4-like phages were screened for possible functional insertion sites, several fusions with the Lambda stf gene were generated and their host range screened.
  • the DTF of the phage (WW13) was used as a testbed.
  • This phage possesses a classical T4-like architecture, with a proximal and a distal tail fiber separated by hinge connectors, a gp38 chaperone/adhesin (to assist folding of the tail fiber and recognition of the host (Trojet et al., 2011, Genome Biol. Evol. 3:674-686) and a gp57A chaperone known to be needed for proper folding of the tail fiber (Matsui et al., 1997, J.
  • FIG. 7 depicts the architecture of an engineered lambda stf-T4-like DTF chimera.
  • the semicircles denote RBS sites; the T sign, a transcriptional terminator; the arrow, a promoter.
  • Several parts of the C-terminus of the DTF were screened and fused to the lambda stf gene at the GAGENS (SEQ ID NO: 252) insertion site.
  • Several variants of the chimera lambda stf-WW13 were functional, as assessed by production of phagemid particles and transduction of a chloramphenicol marker in a collection of E. coli strains. The functional chimeras shown in FIG.
  • FIG. 8 depicts screening of phagemid particles with chimeric lambda stf-T4-like DTFs.
  • Left panel represents wild-type lambda stf; the middle panel represents chimeric lambda-stf-WW13; and the right panel, represents chimeric lambda-stf-PP-1.
  • the insertion sites found for WW13 do not always exist in a given T4-like DTF, thereby complicating the analysis.
  • Another functional insertion site without homology to WW13 was discovered for a second phage (WW55, FIG. 9 ).
  • the same TPGEL insertion site could be found in a subset of T4-like phages and proven to yield functional chimeras with at least one of them, WW34 ( FIG. 9 ), and at MDETNR (SEQ ID NO: 250) insertion site in lambda stf.
  • FIG. 9 shows screening of phagemid particles with chimeric lambda stf-T4-like DTFs.
  • the left panel represents wild-type lambda stf; the middle panel represents chimeric lambda-stf-WW55; and the right panel represents chimeric lambda-stf-WW34.
  • T4-like DTF proteins may or may not share common sites for insertion, attempts were made to identify a universal insertion site that exists in all T4-like DTFs. When several T4-like DTFs are aligned, no homology along the whole DTF gene present in all the sequences exists, except for the N-terminus which is well conserved. The N-terminus of the DTF is thought to interact with the hinge connectors for attachment to the main phage particle.
  • the present disclosure is useful for the generation of phage and phagemid particles with altered host ranges, since it provides a practical framework for the construction of chimeras using the DTFs from any T4-like phage, highlighting its modularity and translatability.
  • the human microbiome comprises different zones of the body, including gut, skin, vagina and mouth [29].
  • the microbiota in these areas is composed of different communities of microorganisms, such as bacteria, archaea and fungi [29]-[31]. While numerous studies have been made that try to elucidate the specific composition of these communities, it is becoming clear that while there may exist a “core microbiome”, there are many variations in the relative content of each microorganism depending on several factors, such as geographical location, diet or age [32]-[35].
  • packaged phagemids are of great interest, since they do not kill the host (unless their payload carries genes aimed at killing the host), payload does not replicate and expand and does not contain any endogenous phage genes.
  • a diagnostic study would be needed to identify the specific serotypes/variants of bacteria that exist in the patient before the treatment in order to find or design a packaged phagemid that allows for delivery of a payload adding a function to the target bacteria without killing them.
  • engineered delivery vehicles that are able to recognize a large number of strains belonging to different serotypes and phylogenetic groups (i.e., engineered particles having a “broad host range”), with a focus on Escherichia coli .
  • engineered particles having a “broad host range” i.e., engineered particles having a “broad host range”
  • a therapeutic delivery approach does not need a priori to reach a large percentage of bacteria; the delivery needs to be high enough for the therapeutic payload to be expressed at the correct levels, which may be highly variable depending on the application.
  • the payload can be expressed by different serotypes or phylogenetic groups. This approach increases the chance that the particle will deliver a payload expressed in vivo in the majority of patients.
  • delivery vehicles were engineered to contain chimeric side tail fibers (stf) that have been selected due to their ability to recognize a large variety of target strains.
  • stf chimeric side tail fibers
  • the ECOR collection is a set of strains isolated from different sources that is thought to represent the variability of this bacterium in Nature [42]. Some phage have been shown to have a broad host range against this collection (for instance, about 53% of the ECOR strains can be lysed with phage AR1 [43] and about 60% with phage SU16 [44]). As opposed to this, a single phage is able to infect 95% of Staphylococcus aureus strains [40].
  • some stf s can be considered as broad host range because the delivery efficiency in the selected ECOR strains is significantly higher than when using the wild type stf. For example, for stf EB6 or stf 68B, about 50% of the strains show medium to high delivery efficiencies, as compared to 17.5% of the strains with the wild type stf. These stf are good candidates for in vivo delivery, since they are able to deliver in different phylogenetic groups as well as serotypes. At the bottom of the Table in FIG.
  • a bar-formatted representation for density scores higher than 3 is shown, where the threshold for a broad host range stf is set at an increase of at least 2 ⁇ compared to the basal line of the wild type stf; this is, stf that are able to deliver with scores of 3 and higher in at least 35% of the strains.
  • Other stf also show an increased delivery as compared to the wild type stf, so a less stringent threshold was set for stf able to deliver with scores 3 or higher with at least a 50% increase compared to the number of strains delivered with the wild-type stf (this is, delivery with scores of 3 and higher in at least 26.25% of the strains).

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Abstract

The present disclosure relates generally to bacterial delivery vehicles for use in efficient transfer of a desired payload into a target bacterial cell. More specifically, the present disclosure relates to bacterial delivery vehicles with desired host ranges based on the presence of a chimeric receptor binding protein (RBP) composed of a fusion between the N-terminal region of a RBP derived from a lambda-like bacteriophage and the C-terminal region of a different RBP.

Description

CROSS-REFERENCE TO RELATED APPLICATION
This application is a divisional application of U.S. patent application Ser. No. 16/816,675, filed Mar. 12, 2020, which issued as U.S. Pat. No. 11,236,133, which is a continuation application of U.S. patent application Ser. No. 16/696,769, filed Nov. 26, 2019, which claims benefit and priority to U.S. Provisional Application No. 62/771,761, filed Nov. 27, 2018; and U.S. Provisional Application No. 62/802,777, filed Feb. 8, 2019, which are both incorporated herein by reference in their entireties.
REFERENCE TO SEQUENCE LISTING SUBMITTED VIA EFS-WEB
This application includes an electronically submitted sequence listing in .txt format. The .txt file contains a sequence listing entitled “2643-3 US TRK-1_ST25.txt” created on Mar. 9, 2020 and is 940,581 bytes in size. The sequence listing contained in this .txt file is part of the specification and is hereby incorporated by reference herein in its entirety.
TECHNICAL FIELD
The present disclosure relates generally to bacterial delivery vehicles for use in efficient transfer of a desired payload into a target bacterial cell. More specifically, the present disclosure relates to bacterial delivery vehicles with desired host ranges based on the presence of a chimeric receptor binding protein (RBP) composed of a fusion between the N-terminal region of a RBP derived from a lambda-like, or lambda bacteriophage and the C-terminal region of a different RBP.
BACKGROUND
Bacteriophages are parasites that infect and multiply in bacteria. In general, the infection process can be divided in several stages: (i) adsorption corresponding to recognition and binding to the bacterial cell; (ii) injection of the DNA genome into the bacterial cell cytoplasm; (iii) production of a set of viral proteins that can lead to insertion in the host target genome (lysogenic phages) or to the production of infective particles (lytic phages) and (iv) release of mature virions from the infected cell, usually by controlled lysis [1].
Being the first step necessary for a successful infection, recognition and binding to the target cell is an essential process in the bacteriophage life cycle. Bacteriophages can in some cases recognize several strains of the same species, having a “broad host range”, but very commonly are able to recognize a specific antigen present only on some strains of the same species [2]. It is thus not surprising that this step of the infection process is central in the competition between bacteriophage and bacteria for successful infection.
As a general mechanism, a bacteriophage encodes two main sets of proteins that are involved in the recognition process. The first set is able to attach to the bacteriophage's primary receptor on the cell surface, an event that triggers DNA ejection into the cytoplasm and is usually viewed as an “irreversible” binding process [3]. Different bacteriophage genera differ in the organization of this set of proteins, and hence the naming can be different. In some Siphovirus, for example, they are called the “central tail fiber” or “tail tip”, which binds irreversibly to the LamB receptor in Escherichia coli. In the siphoviridae lambda, the “central tail fiber” or “tail tip” is composed of the protein gpJ [4]. In some other Siphovirus, like T5, a protein located at the very tip of the tail mediates this process. In the case of T5, a protein called pb5 recognizes the FhuA receptor [5]. This type of protein can be found in many other bacteriophages. In Myoviruses, like T4, the irreversible binding to the primary receptor or to the cell surface in general is mediated by the “short tail fibers”, which are also located at the end of the tail tube [5].
The second set of proteins in the bacteriophage (herein referred to as “receptor binding proteins”) encodes recognition and binding activities to the so-called “secondary receptor” on the bacterium. This secondary receptor allows for transient binding of the phage particle on the cell surface in order to scan the surface and position the first set of proteins in contact with the primary receptor. Since this binding is reversible, it allows the phage to “walk” on the cell surface until a primary receptor is found and the infection process starts. These protein complexes are sometimes referred to as “L-shape fibers”, such as in T5, “side tail fibers” such as in lambda, “long tail fibers” as in T4, or tailspikes such as in phage P22 [5]-[8]. For some phages, the presence of this second set of proteins is necessary for the infection process to occur, such as T4 [5]. In some other phages, like lambda, this second set of proteins is not strictly necessary for the infection process to happen, but it may allow for a more efficient binding to the target cell [7].
Since the adsorption process is strictly necessary for a successful infection to happen, bacteria can develop multiple ways to avoid being recognized by a bacteriophage. For example, they can mutate the primary or secondary receptor to which the bacteriophage binds; they can mask this receptor by attaching proteins to it (receptor masking); or they can grow physical barriers around them in the form of bacterial capsules, thus blocking any access to the cell surface [9]. Bacteria can produce many different types of extracellular polymeric capsules [10]. In turn, bacteriophages have evolved different strategies to bypass these defense mechanisms. For instance, mutating the tail tip proteins allows them to use a different receptor [11]. However, the presence of a polymeric capsule around the bacterium requires a different approach, as it blocks all contact to any receptors on the cell surface. In these cases, bacteriophages have evolved specific proteins that can enzymatically degrade this capsule to gain access to the cells. These depolymerase activities are encoded in protein complexes that are distinct to the primary receptor recognition machinery, in the form of side tail fibers, long tail fibers or tailspikes [12], [13], [14].
The concept of a bacteriophage's host range needs to be redefined when only the adsorption and injection processes are taken into account. Since all incompatibilities or defense mechanisms related to the phage replication cycle are left out of the picture, the “adsorption host range” of a given phage is usually larger than the “classical host range” in which the infectious cycle leads to newly produced mature virions. The concept of host range becomes even more different to the classical definition when packaged phagemids based on a given bacteriophage capsid is used. Packaged phagemids do not contain the information necessary to replicate the viral particles, because they do not package their cognate viral genome. Thus, the host range of a packaged phagemid tends to be larger than that of the parental bacteriophage it derives from. Therefore, for development of novel bacterial delivery vehicles, designed for the efficient delivery of exogenous DNA payload into target strains, it is of utmost importance to be able to engineer delivery vehicles with desired host ranges as well as the ability to bypass bacterial mechanisms that can lead to unsuccessful binding of the packaged phagemid to the bacterial cell surface.
SUMMARY
As a general mechanism, a bacteriophage encodes sets of proteins that are involved in the bacterial cell recognition process. Described herein are novel approaches to engineering synthetic bacterial delivery vehicles with desired target host ranges. In some aspects, synthetic bacterial delivery vehicles are provided that are characterized by a chimeric receptor binding protein (RBP), wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different bacteriophage RBP. Such bacteriophage RBPs, from which the chimeric RBP are derived, include, for example, and depending on phages families, “L-shape fibers”, “side tail fibers (stfs)”, “long tail fibers” or “tailspikes.” As disclosed herein, it has been demonstrated that a significant portion of a lambda-like bacteriophage receptor binding protein (RBP), such as a stf protein, can be exchanged with a portion of a different RBP. Moreover, specific fusion positions in the RBPs have been identified which allow one to obtain functional chimeric RBPs.
The chimeric receptor binding protein (RBP) is one wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal RBP with reference to the lambda stf sequence (SEQ ID NO: 1) or a similar region of a RBP having homology with one or more of three amino acid regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda stf sequence. In one specific aspect of the invention, the different RBP domain of the chimeric receptor binding protein (RBP) is derived from any bacteriophage or from any bacteriocin.
In one specific aspect, the RBP from the lambda-like bacteriophage, or the lambda bacteriophage, or the different RBP contains homology in one or more of three amino acid regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1). In certain aspects, the homology between the lambda-like bacteriophage, the lambda bacteriophage, or the different RBP and the one or more of three amino acids regions is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, and around 90% identity for 18 amino acids or more with reference to the lambda bacteriophage stf sequence (SEQ ID NO:1). Determination of homology can be performed using alignment tools such as the Smith-Waterman algorithm (Smith et al., 1981, J. Mol. Biol 147:195-197) or EMBOSS Matcher (Rice, Longden, Bleasby 2000 EMBOSS Trends in Genetics 16: 276-277).
In one aspect of the invention, the chimeric RBP comprises the N-terminal domain of a RBP fused to the C-terminal domain of a different RBP within one of the amino acid regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO:1). In another embodiment of the invention, the chimeric RBP comprises an N-terminal domain and a C-terminal domain fused within one of the amino acids regions selected from positions 1-150, 320-460 or 495-560 at an insertion site having at least 80% identity with an insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO: 248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251) and, GAGENS (SEQ ID NO: 252).
In another aspect, the chimeric RBP comprises the N-terminal domain of a RBP fused to the C-terminal domain of different RBP wherein the different RBP is a protein or group a different proteins that confers an altered host range. In one embodiment, the different RBP is a T4-like or T4 long tail fiber composed of a proximal tail fiber and a distal tail fiber (DTF), and the C-terminal domain of a T4-like or T4 RBP is the distal tail fiber (DTF). In another embodiment, the N-terminal domain of a RBP is fused to the T4-like or T4 distal tail fiber at an insertion site within the T4-like or T4 DTF having at least 80% identity with an insertion site selected from the group consisting of amino acids ATLKQI (SEQ ID NO: 253), IIQLED (SEQ ID NO: 254), GNIIDL (SEQ ID NO: 255), IATRV (SEQ ID NO: 256), TPGEL (SEQ ID NO: 257), GAIIN (SEQ ID NO: 258), NQIID (SEQ ID NO: 259), GQIVN (SEQ ID NO: 260) and, VDRAV (SEQ ID NO: 261). In a specific embodiment, the N-terminal domain of a RBP is fused to the T4-like or T4 distal tail fiber within a region from amino acid 1 to 90, with a preferred region from amino acid 40 to 50 of the DTF.
In specific embodiments, the disclosure provides specific chimeric RBPs. SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs as well as, in some instances, their corresponding natural chaperone proteins (designated “AP”). Such AP proteins assist in the folding of the chimeric RBPs. In a specific embodiment, the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 123-129, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246.
In another aspect, the present disclosure provides nucleotide sequences encoding for the chimeric RBPs disclosed herein. In a specific embodiment, nucleic acids encoding such chimeric RBPs, as well as their corresponding AP proteins, are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210 and 212-213. In a specific embodiment, the nucleic acids encoding such chimeric RBPs comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172 175, 182, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
In one specific non-limiting aspect of the invention, it has been demonstrated that engineering the chimeric RBP to encode depolymerase activity can dramatically increases the delivery efficiency of the provided bacterial delivery vehicles comprising the chimeric RBP disclosed herein. In an embodiment of the invention, the different RBP domain of the chimeric RPB comprises depolymerase activity against an encapsulated bacterial strain. In a specific embodiment, the depolymerase is an endosialidase such as, for example, a K1F or K5 endosialidase.
In an embodiment of the invention, nucleic acid molecules encoding the chimeric RBPs disclosed herein are provided. Such nucleic acids may be included in vectors such as bacteriophages, plasmids, phagemids, viruses, and other vehicles which enable transfer and expression of the chimeric RBP encoding nucleic acids.
Bacterial delivery vehicles are provided which enable transfer of a nucleic acid payload, encoding a protein or nucleic acid of interest, into a desired target bacterial host cell. Such bacterial delivery vehicles are characterized by having a chimeric RBP comprising a fusion between the N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and the C-terminal domain of a different RBP. In an embodiment of the invention, the bacterial delivery vehicles contain a chimeric RBP comprising a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal domain with reference to the lambda stf sequence (SEQ ID NO: 1). In one aspect, the RBP from the lambda-like bacteriophage, the lambda bacteriophage, and the different RBP contain homology in one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1). In certain aspects, the homology is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, or around 90% identity for 18 amino acids or more within the one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence. In one specific aspect of the invention, the different RBP domain of the chimeric receptor binding protein (RBP) is derived from a bacteriophage or a bacteriocin. In one aspect of the invention, the chimeric RBP comprises an N-terminal domain of a RBP fused to a C-terminal domain of a RBP within one of the amino acids regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP domain with reference to the lambda stf sequence. In another embodiment of the invention, the chimeric RBP comprises an N-terminal domain of a RBP and a C-terminal domain of a RBP fused within a site of the N-terminal RBP domain having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO: 248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
In specific embodiments, the disclosure provides a bacterial delivery vehicle comprising a chimeric RBP. SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs and in addition, in some instances, their corresponding natural chaperone proteins (designated “AP”). Such AP proteins assist in the folding of the chimeric RBPs. In a specific embodiment, the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 130, 131, 132, 135, 138, 139, 142, 145, 148,151, 216, 219, 221, 223, 227, 230, 232, 234,236, 238, 240, 243, 245 or 246.
In one aspect, the present disclosure also provides nucleotide sequences encoding for the chimeric RBPs disclosed herein. In a specific embodiment, nucleic acids encoding such chimeric RBPs, as well as corresponding AP proteins, are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210 and 212-213. In a specific embodiment, the nucleic acids encoding such chimeric RBPs comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172, 175, 182, 185, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
In other specific embodiments and to increase the delivery efficiency of the bacterial delivery vehicles disclosed herein the different RBP domain of the chimeric RBP comprises a domain having depolymerase activity against an encapsulated bacterial strain. In a specific embodiment, the depolymerase is an endosialidase, such as for example, a K1F or K5 endosialidase.
The bacterial delivery vehicles provided herein enable transfer of a nucleic acid payload, encoding one or more protein or nucleic acid of interest, into a desired target bacterial host cell. In certain embodiments of the invention, the nucleic acid of interest is selected from the group consisting of a Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme such as a nuclease or a kinase, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor, a membrane protein, a structural protein, a secreted protein, a gene expressing resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any of their combination. In an embodiment of the invention, the nucleic acid payload encodes a therapeutic protein. In another embodiment, the nucleic acid payload encodes an anti-sense nucleic acid molecule. In some embodiment, the nucleic acid payload encodes 2 nucleic acid of interest, one being a nuclease gene, for instance a Cas nuclease gene, and one being any other nucleic acid of interest. In one aspect, the bacterial delivery vehicle enables the transfer of a nucleic acid payload that encodes a nuclease that targets cleavage of a host bacterial cell genome or a host bacterial cell plasmid. In some aspects, the cleavage occurs in an antibiotic resistant gene. In another embodiment of the invention, the nuclease mediated cleavage of the host bacterial cell genome is designed to stimulate a homologous recombination event for insertion of a nucleic acid of interest into the genome of the bacterial cell.
The present invention also provides pharmaceutical or veterinary compositions comprising one or more of the bacterial delivery vehicles disclosed herein and a pharmaceutically-acceptable carrier. Also provided is a method for treating a bacterial infection comprising administering to a subject having a bacterial infection in need of treatment the provided pharmaceutical or veterinary composition. A method for reducing the amount of virulent and/or antibiotic resistant bacteria in a bacterial population is provided comprising contacting the bacterial population with the bacterial delivery vehicles disclosed herein.
BRIEF DESCRIPTION OF FIGURES
In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example, with reference to the accompanying drawings. With specific reference to the drawings, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention
FIG. 1 demonstrates delivery in wild-type E. coli strains with lambda and OMPF-lambda packaged phagemids. Lambda packaged phagemids were diluted 1:5 in LB plus 5 mM CaCl2 and 10 uL added in each well. 90 uL of cells grown to an OD600 of around 0.5 were then added to each phagemid-containing well, incubated for 30 min at 37° C. and 10 uL spotted on LB-agar supplemented with chloramphenicol. Left panel, wild type lambda packaged phagemids; right panel, OMPF-lambda variant. Arrows show strains with modified delivery as compared to lambda wild-type.
FIG. 2 depicts wild-type lambda and lambda-stf-K1F chimeric delivery vehicles on K1+strains. Lambda packaged phagemids were sequentially diluted 10× in LB plus 5 mM CaCl2 and 10 uL added in each well. Cells grown to an OD600 of around 0.5 were then added to each phagemid dilution, incubated for 30 min at 37° C. and 10 uL plated on LB supplemented with chloramphenicol. Top panel, strain UTI89; bottom panel, strain S88. Left plates, wild type lambda packaged phagemids; right plates, stf-K1F lambda packaged phagemids.
FIG. 3 depicts wild-type lambda and lambda-stf-K5 chimeric delivery vehicles on a K5+ strain. Lambda packaged phagemids were sequentially diluted 10× in LB plus 5 mM CaCl2 and 10 uL added in each well. ECOR55 grown to an OD600 of around 0.5 were then added to each phagemid dilution, incubated for 30 min at 37° C. and 10 uL plated on LB supplemented with chloramphenicol. Left panel, wild type lambda packaged phagemids; right panel, stf-K15 lambda packaged phagemids.
FIG. 4 depicts wild-type lambda, lambda-stf-AG22 and lambda-stf-SIEA11 chimeric delivery vehicles on a variety of encapsulated strains (O and K capsules). Lambda phagemids were diluted 1:5 in LB plus 5 mM CaCl2 and 10 uL added in each well. 90 uL of cells grown to an OD600 of around 0.5 were then added to each phagemid-containing well, incubated for 30 min at 37° C. and 10 uL spotted on LB-agar supplemented with chloramphenicol. Left panel, wild type lambda phagemids; middle panel, lambda stf-SIEA11 variant; right panel, lambda-stf-AG22 variant. Arrows show strains with modified delivery as compared to lambda wild-type.
FIG. 5A-C demonstrates delivery of wild-type lambda and stf chimeras with different insertion sites on a variety of encapsulated strains (0 and K capsules). Lambda packaged phagemids were diluted 1:5 in LB plus 5 mM CaCl2 and 10 uL added in each well. 90 uL of cells grown to an OD600 of around 0.5 were then added to each phagemid-containing well, incubated for 30 min at 37° C. and 10 uL spotted on LB-agar supplemented with chloramphenicol. FIG. 5(A) Left panel, wild type lambda packaged phagemids; rest of panels, three different ADAKKS-stf variants. FIG. 5(B) Left panel, wild type lambda packaged phagemids; rest of panels, three different SASAAA-stf variants. FIG. 5(C) Left panel, wild type lambda packaged phagemids; rest of panels, three different MDETNR-stf variants. For all panels, arrows show strains with improved delivery efficiency as compared to lambda wild-type.
FIG. 6 depicts a phmmer search that was performed with a 50aa sliding window (step 10) on the representative proteome database (rp75). The number of significant hits (E-value<0.01) is reported.
FIG. 7. depicts architecture of the engineered lambda stf-T4-like DTF chimera. The semicircles denote RBS sites; the T sign, a transcriptional terminator; the arrow, a promoter.
FIG. 8. shows screening of phagemid particles with chimeric lambda stf-T4-like DTFs. A collection of 96 different wild type E. coli strains, encompassing different serotypes, was transduced with lambda-based phagemids and plated on Cm LB agar. Left panel, wild-type lambda stf; middle panel, chimeric lambda-stf-WW13; right panel, chimeric lambda-stf-PP-1.
FIG. 9. demonstrates screening of phagemid particles with chimeric lambda stf-T4-like DTFs. A collection of 96 different wild type E. coli strains, encompassing different serotypes, was transduced with lambda-based phagemids and plated on Cm LB agar. Left panel, wild-type lambda stf; middle panel, chimeric lambda-stf-WW55; right panel, chimeric lambda-stf-WW34.
FIG. 10. depicts screening of phagemid particles with chimeric lambda stf-T4-like DTFs. All points shown refer to the universal insertion site of the DTF, located within aminoacid range from position 1 to 90 with reference to WW13 aminoacid sequence. A collection of 96 different wild type E. coli strains, encompassing different serotypes, was transduced with lambda-based phagemids and plated on Cm LB agar (names on top).
FIG. 11. depicts dot scoring system to quantify delivery efficiency. Density 0, 5 or fewer colonies; density 1, more than 5 colonies but not enough to define a clear circular drop; density 2, several colonies, but the background is clearly visible and some colonies are still separated; density 3, many colonies, the background is still visible but the colonies are hardly discernible as separate; density 4, spot almost completely dense, the background can only be seen faintly in some parts of the drop; density 5, spot looks completely dense, background cannot be seen.
FIG. 12-1, FIG. 12-2, and FIG. 12-3 depicts raw dot titrations of delivery particles with chimeric stf in 40 human strains of the ECOR collection. Below each panel, the name of the chimeric stf. Above each dot, the 1-2 letter code used to identify strains in FIG. 13.
DETAILED DESCRIPTION
Disclosed herein are novel approaches to engineering synthetic bacterial delivery vehicles with desired target host ranges. The synthetic bacterial delivery vehicles are characterized by a chimeric receptor binding protein (RBP), wherein the chimeric RBP comprises a fusion between the N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and the C-terminal domain of a different RBP. It has been demonstrated herein that a significant portion of a lambda-like RBP, such as a stf protein, can be exchanged with a portion of a different RBP. Moreover, specific fusion positions of the receptor binding protein have been identified which allow one to obtain a functional chimeric RBP.
As used herein, a receptor binding protein or RBP is a polypeptide that recognizes, and optionally binds and/or modifies or degrades a substrate located on the bacterial outer envelope, such as, without limitation, bacterial outer membrane, LPS, capsule, protein receptor, channel, structure such as the flagellum, pili, secretion system. The substrate can be, without limitation, any carbohydrate or modified carbohydrate, any lipid or modified lipid, any protein or modified protein, any amino acid sequence, and any combination thereof. As used herein, a lambda-like bacteriophage refers to any bacteriophage encoding a RBP having amino acids sequence homology of around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, or around 90% identity for 18 amino acids or more in one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 with reference to the lambda bacteriophage stf sequence of SEQ ID NO: 1, independently of other amino acids sequences encoded by said bacteriophage.
The present disclosure provides a chimeric receptor binding protein (RBP), wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different bacteriophage RBP. Such bacteriophage RBPs, from which the chimeric RBP are derived, include, for example, “L-shape fibers”, “side tail fibers (stfs)”, “long tail fibers” or “tailspikes.” As disclosed herein, it has been demonstrated that a significant portion of a lambda-like bacteriophage receptor binding protein (RBP), such as a stf protein, can be exchanged with a portion of a different RBP. Moreover, specific fusion positions in the RBPs have been identified which allow one to obtain a functional chimeric RBP. Such chimeric RBPs include those having an altered host range and/or biological activity such as, for example, depolymerase activity.
The chimeric receptor binding protein (RBP) is one wherein the chimeric RBP comprises a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal RBP with reference to the lambda stf sequence (SEQ ID NO: 1) or a similar region of a RBP having homology with one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda stf sequence. In one specific aspect of the invention, the different RBP of the chimeric receptor binding protein (RBP) is derived from any bacteriophage or from any bacteriocin.
In one specific aspect, the RBP from the lambda-like bacteriophage, the lambda bacteriophage, or the different RBP contain homology with one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO:1). In certain aspects, the homology between the lambda-like bacteriophage, the lambda bacteriophage, or the different RBP and the one or more amino acids regions is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, and around 90% identity for 18 amino acids or more. Determination of homology can be performed using alignment tools such as the Smith-Waterman algorithm (Smith et al., 1981, J. Mol. Biol 147:195-197) or EMBOSS Matcher (Rice, Longden, Bleasby 2000 EMBOSS Trends in Genetics 16: 276-277). In one aspect of the invention, the chimeric RBP comprises the N-terminal domain of the chimeric RBP fused to the C-terminal domain of the chimeric RBP within one of the amino acids regions selected from positions 80-150, 320-460, or 495-560 with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1). In another embodiment of the invention, the chimeric RBP comprises an N-terminal domain and a C-terminal domain fused within one the three amino acids regions at an insertion site having at least 80% identity with an insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO: 248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
In specific embodiments, the invention provides chimeric RBPs. SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs and in addition, in some instances, their corresponding natural chaperone proteins (designated “AP”). Such AP proteins assist in the folding of the chimeric RBPs. In a specific embodiment, the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234,236, 238, 240, 243, 245 or 246
In one aspect, the present disclosure also provides nucleotide sequences encoding for the chimeric RPBs disclosed herein. In a specific embodiment, nucleic acids encoding such chimeric RBPs, as well as corresponding AP proteins, are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210, 212-213. In a specific embodiment, the nucleic acids encoding the chimeric RBP comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172, 175 182, 185, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
In one specific non-limiting aspect of the invention, it has been demonstrated that engineering the chimeric RBP to encode depolymerase activity can dramatically increases the delivery efficiency of the provided bacterial delivery vehicles comprising the chimeric RBP disclosed herein. In an embodiment of the invention, the different RBP domain of the chimeric RPB comprises depolymerase activity against an encapsulated bacterial strain. In a specific embodiment, the depolymerase is an endosialidase such as, for example, a K1F or K5 endosialidase.
Nucleic acid molecules encoding the chimeric RBPs disclosed herein are provided. Such nucleic acids may be included in vectors such as bacteriophages, plasmids, phagemids, viruses, and other vehicles which enable transfer and expression of the chimeric RBP encoding nucleic acids.
Bacterial delivery vehicles are provided which enable transfer of a nucleic acid payload, encoding a protein or nucleic acid of interest, into a desired target bacterial host cell. Such bacterial delivery vehicles are characterized by having a chimeric RBP comprising a fusion between the N-terminal domain of a RBP from a lambda-like bacteriophage, or lambda bacteriophage, and the C-terminal domain of a different RBP. In an embodiment of the invention, the bacterial delivery vehicles contain a chimeric RBP comprising a fusion between an N-terminal domain of a RBP derived from a lambda-like bacteriophage, or lambda bacteriophage, and a C-terminal domain of a different RBP wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain of a different RBP within one of the amino acids regions selected from positions 1-150, 320-460, or 495-560 of the N-terminal domain RBP with reference to the lambda stf sequence (SEQ ID NO: 1). In one aspect, the RBP from the lambda-like bacteriophage, the lambda bacteriophage, and the different RBP contain homology in one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the N-terminal RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1). In certain aspects, the homology is around 35% identity for 45 amino acids or more, around 50% identify for 30 amino acids or more, or around 90% identity for 18 amino acids or more within the one or more of three amino acids regions ranging from positions 1-150, 320-460, and 495-560 of the N-terminal RBP with reference to the lambda bacteriophage stf sequence (SEQ ID NO: 1). In one specific aspect of the invention, the different RBP domain of the chimeric receptor binding protein (RBP) is derived from a bacteriophage or a bacteriocin. In one aspect of the invention, the chimeric RBP comprises an N-terminal domain of a RBP fused to a C-terminal domain of a RBP within one of the amino acids regions selected from 80-150, 320-460, or 495-560 of the RBPs with reference to the lambda stf sequence (SEQ ID NO: 1). In another embodiment of the invention, the chimeric RBP comprises an N-terminal domain of a RBP and a C-terminal domain of a RBP fused within a site of the N-terminal RBPs having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO. 248), ADAKKS (SEQ ID NO. 249), MDETNR (SEQ ID NO. 250), SASAAA (SEQ ID NO. 251), and GAGENS (SEQ ID NO. 252).
In specific embodiments, the disclosure provides a bacterial delivery vehicle comprising a chimeric RBP. SEQ ID NOS 2-61, 123-153, 216-244 and 246-247 disclose the amino acid sequences of such chimeric RBPs and in addition, in some instances, their corresponding natural chaperone proteins (designated “AP”). Such AP proteins assist in the folding of the chimeric RBPs. In a specific embodiment, the RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 130, 131, 132, 135, 138, 139, 142, 145, 148 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246
In one aspect, the present disclosure also provides nucleotide sequences encoding for the chimeric RPBs disclosed herein. In a specific embodiment, nucleic acids encoding such chimeric RBPs, as well as corresponding AP proteins, are depicted in SEQ ID NOS 62-120, 122, 154-177, 182-210, 212-213. In a specific embodiment, the nucleic acids encoding the chimeric RBPs comprise the nucleotide sequence of SEQ ID NO: 62, 64, 67, 69, 72, 75, 77, 80, 83, 84, 85, 87, 89, 91, 93, 95, 97, 99, 101, 102, 104, 106, 107, 108, 109, 110, 111, 112, 113, 116, 119, 154, 155, 156, 159, 162, 163, 166, 169, 172, 175, 182, 185, 187, 189, 193, 196, 198, 200, 202, 204, 206, 209 or 212.
In other specific embodiments and to increase the delivery efficiency of the bacterial delivery vehicles disclosed herein the different RBP domain of the chimeric comprises a domain having depolymerase activity against an encapsulated bacterial strain. In a specific embodiment, the depolymerase is an endosialidase, such as for example, a K1F or K5 endosialidase.
The bacterial delivery vehicles provided herein enable transfer of a nucleic acid payload, encoding a protein or nucleic acid of interest, into a desired target bacterial host cell. As used herein, the term “delivery vehicle” refers to any means that allows the transfer of a payload into a bacterium. There are several types of delivery vehicles encompassed by the present invention including, without limitation, bacteriophage scaffold, virus scaffold, chemical based delivery vehicle (e.g., cyclodextrin, calcium phosphate, cationic polymers, cationic liposomes), protein-based or peptide-based delivery vehicle, lipid-based delivery vehicle, nanoparticle-based delivery vehicles, non-chemical-based delivery vehicles (e.g., transformation, electroporation, sonoporation, optical transfection), particle-based delivery vehicles (e.g., gene gun, magnetofection, impalefection, particle bombardment, cell-penetrating peptides) or donor bacteria (conjugation).
Any combination of delivery vehicles is also encompassed by the present invention. The delivery vehicle can refer to a bacteriophage derived scaffold and can be obtained from a natural, evolved or engineered capsid. In some embodiments, the delivery vehicle is the payload as bacteria are naturally competent to take up a payload from the environment on their own.
As used herein, the term “payload” refers to any one or more nucleic acid sequence and/or amino acid sequence, or a combination of both (such as, without limitation, peptide nucleic acid or peptide-oligonucleotide conjugate) transferred into a bacterium with a delivery vehicle. The term “payload” may also refer to a plasmid, a vector or a cargo. The payload can be a phagemid or phasmid obtained from natural, evolved or engineered bacteriophage genome. The payload can also be composed only in part of phagemid or phasmid obtained from natural, evolved or engineered bacteriophage genome.
As used herein, the term “nucleic acid” refers to a sequence of at least two nucleotides covalently linked together which can be single-stranded or double-stranded or contains portion of both single-stranded and double-stranded sequence. Nucleic acids of the present invention can be naturally occurring, recombinant or synthetic. The nucleic acid can be in the form of a circular sequence or a linear sequence or a combination of both forms. The nucleic acid can be DNA, both genomic or cDNA, or RNA or a combination of both. The nucleic acid may contain any combination of deoxyribonucleotides and ribonucleotides, and any combination of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xathanine, hypoxathanine, isocytosine, 5-hydroxymethylcytosine and isoguanine. Other examples of modified bases that can be used in the present invention are detailed in Chemical Reviews 2016, 116 (20) 12655-12687. The term “nucleic acid” also encompasses any nucleic acid analogs which may contain other backbones comprising, without limitation, phosphoramide, phosphorothioate, phosphorodithioate, O-methylphophoroamidite linkage and/or deoxyribonucleotides and ribonucleotides nucleic acids. Any combination of the above features of a nucleic acid is also encompassed by the present invention.
Origins of replication known in the art have been identified from species-specific plasmid DNAs (e.g. CoIE1, R1, pT181, pSC101, pMB1, R6K, RK2, p15a and the like), from bacterial virus (e.g. φX174, M13, F1 and P4) and from bacterial chromosomal origins of replication (e.g. oriC). In one embodiment, the phagemid according to the disclosure comprises a bacterial origin of replication that is functional in the targeted bacteria.
Alternatively, the plasmid according to the disclosure does not comprise any functional bacterial origin of replication or contain an origin of replication that is inactive in the targeted bacteria. Thus, the plasmid of the disclosure cannot replicate by itself once it has been introduced into a bacterium by the bacterial virus particle.
In one embodiment, the origin of replication on the plasmid to be packaged is inactive in the targeted bacteria, meaning that this origin of replication is not functional in the bacteria targeted by the bacterial virus particles, thus preventing unwanted plasmid replication.
In one embodiment, the plasmid comprises a bacterial origin of replication that is functional in the bacteria used for the production of the bacterial virus particles.
Plasmid replication depends on host enzymes and on plasmid-controlled cis and trans determinants. For example, some plasmids have determinants that are recognized in almost all gram-negative bacteria and act correctly in each host during replication initiation and regulation. Other plasmids possess this ability only in some bacteria (Kues, U and Stahl, U 1989 Microbiol Rev 53:491-516).
Plasmids are replicated by three general mechanisms, namely theta type, strand displacement, and rolling circle (reviewed by Del Solar et al. 1998 Microhio and Molec Biol. Rev 62:434-464) that start at the origin of replication. These replication origins contain sites that are required for interactions of plasmid and/or host encoded proteins.
Origins of replication used on the plasmid of the disclosure may be of moderate copy number, such as colEl ori from pBR322 (15-20 copies per cell) or the R6K plasmid (15-20 copies per cell) or may be high copy number, e.g. pUC oris (500-700 copies per cell), pGEM oris (300-400 copies per cell), pTZ oris (>1000 copies per cell) or pBluescript oris (300-500 copies per cell).
In one embodiment, the bacterial origin of replication is selected in the group consisting of ColE1, pMB1 and variants (pBR322, pET, pUC, etc), p15a, ColA, ColE2, pOSAK, pSC101, R6K, IncW (pSa etc), IncFII, pT181, P1, F IncP, IncC, IncJ, IncN, IncP1, IncP4, IncQ, IncH11, RSF1010, CloDF13, NTP16, R1, f5, pPS10, pC194, pE194, BBR1, pBC1, pEP2, pWVO1, pLF1311, pAP1, pWKS1, pLS1, pLS11, pUB6060, pJD4, 0E01, pSN22, pAMbetal, pIP501, pIP407, ZM6100(Sa), pCU1, RA3, pMOL98, RK2/RP4/RP1/R68, pB10, R300B, pRO1614, pRO1600, pECB2, pCM1, pFA3, RepFIA, RepFIB, RepFIC, pYVE439-80, R387, phasyl, RA1, TF-FC2, pMV158 and pUB113.
More preferably, the bacterial origin of replication is a E. coli origin of replication selected in the group consisting of ColE1, pMB1 and variants (pBR322, pET, pUC, etc), p15a, ColA, ColE2, pOSAK, pSC101, R6K, IncW (pSa etc), IncFII, pT181, P1, F IncP, IncC, IncJ, IncN, IncP1, IncP4, IncQ, IncH11, RSF1010, CloDF13, NTP16, R1, f5 and pPS10.
More preferably, the bacterial origin of replication is selected in the group consisting of pC194, pE194, BBR1, pBC1, pEP2, pWVO1, pLF1311, pAP1, pWKS1, pLS1, pLS11, pUB6060, pJD4, pIJ101, pSN22, pAMbetal, pIP501, pIP407, ZM6100(Sa), pCU1, RA3, pMOL98, RK2/RP4/RP1/R68, pB10, R300B, pRO1614, pRO1600, pECB2, pCM1, pFA3, RepFIA, RepFIB, RepFIC, pYVE439-80, R387, phasyl, RA1, TF-FC2, pMV158 and pUB113.
Even more preferably, the bacterial origin of replication is ColE1.
The delivered nucleic acid sequence according to the disclosure may comprise a phage replication origin which can initiate, with complementation of a complete phage genome, the replication of the delivered nucleic acid sequence for later encapsulation into the different capsids.
A phage origin of replication comprised in the delivered nucleic acid sequence of the disclosure can be any origin of replication found in a phage.
Preferably, the phage origin of replication can be the wild-type or non-wildtype sequence of the M13, f1, φX174, P4, lambda, P2, lambda-like, HK022, mEP237, HK97, HK629, HK630, mEP043, mEP213, mEP234, mEP390, mEP460, mEPx1, mEPx2, phi80, mEP234, T2, T4, T5, T7, RB49, phiX174, R17, PRD1 P1-like, P2-like, P22, P22-like, N15 and N15-like bacteriophages.
More preferably, the phage origin of replication is selected in the group consisting of phage origins of replication of M13, f1, φX174, P4, and lambda.
In a particular embodiment, the phage origin of replication is the lambda or P4 origin of replication.
The delivered nucleic acid of interest comprises a nucleic acid sequence under the control of a promoter. In certain embodiments of the invention, the nucleic acid of interest is selected from the group consisting of a Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme such as a nuclease or a kinase, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor, a membrane protein, a structural protein, a secreted protein, a gene expressing resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any of their combination. In an embodiment of the invention, the nucleic acid payload encodes a therapeutic protein. In another embodiment, the nucleic acid payload encodes an anti-sense nucleic acid molecule. In some embodiment, the nucleic acid payload encodes 2 nucleic acids of interest, one being a nuclease gene, for instance a Cas nuclease gene, and one being any other nucleic acid of interest.
In one embodiment, the sequence of interest is a programmable nuclease circuit to be delivered to the targeted bacteria. This programmable nuclease circuit is able to mediate in vivo sequence-specific elimination of bacteria that contain a target gene of interest (e.g. a gene that is harmful to humans). Some embodiments of the present disclosure relate to engineered variants of the Type II CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated) system of Streptococcus pyogenes. Other programmable nucleases that can be used include other CRISPR-Cas systems, engineered TALEN (Transcription Activator-Like Effector Nuclease) variants, engineered zinc finger nuclease (ZFN) variants, natural, evolved or engineered meganuclease or recombinase variants, and any combination or hybrids of programmable nucleases. Thus, the engineered autonomously distributed nuclease circuits provided herein may be used to selectively cleave DNA encoding a gene of interest such as, for example, a toxin gene, a virulence factor gene, an antibiotic resistance gene, a remodeling gene or a modulatory gene (cf. WO2014124226).
Other sequences of interest, preferably programmable, can be added to the delivered nucleic acid sequence so as to be delivered to targeted bacteria. Preferably, the sequence of interest added to the delivered nucleic acid sequence leads to cell death of the targeted bacteria. For example, the nucleic acid sequence of interest added to the plasmid may encode holins or toxins.
Alternatively, the sequence of interest circuit added to the delivered nucleic acid sequence does not lead to bacteria death. For example, the sequence of interest may encode reporter genes leading to a luminescence or fluorescence signal. Alternatively, the sequence of interest may comprise proteins and enzymes achieving a useful function such as modifying the metabolism of the bacteria or the composition of its environment.
In a particular embodiment, the nucleic sequence of interest is selected in the group consisting of Cas9, a single guide RNA (sgRNA), a CRISPR locus, a gene expressing an enzyme such as a nuclease or a kinase, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor, a membrane protein, a structural protein, a secreted protein, resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor and a gene expressing a virulence protein or a virulence factor.
In a particular embodiment, the delivered nucleic acid sequence according to the disclosure comprises a nucleic acid sequence of interest that encodes a bacteriocin, which can be a proteinaceous toxin produced by bacteria to kill or inhibit growth of other bacteria. Bacteriocins are categorized in several ways, including producing strain, common resistance mechanisms, and mechanism of killing. Such bacteriocin had been described from gram negative bacteria (e.g. microcins, colicin-like bacteriocins and tailocins) and from gram positive bacteria (e.g. Class I, Class II, Class III or Class IV bacteriocins).
In one embodiment, the delivered nucleic acid sequence according to the disclosure further comprises a sequence of interest encoding a toxin selected in the group consisting of microcins, colicin-like bacteriocins, tailocins, Class I, Class II, Class III and Class IV bacteriocins.
In a particular embodiment, the corresponding immunity polypeptide (i.e. anti-toxin) may be used to protect bacterial cells (Cotter et al., Nature Reviews Microbiology 11: 95, 2013, which is hereby incorporated by reference in its entirety) for delivered nucleic acid sequence production and encapsidation purpose but is absent in the pharmaceutical composition and in the targeted bacteria in which the delivered nucleic acid sequence of the disclosure is delivered.
In one aspect of the disclosure, the CRISPR system is included in the delivered nucleic acid sequence. The CRISPR system contains two distinct elements, i.e. i) an endonuclease, in this case the CRISPR associated nuclease (Cas or “CRISPR associated protein”) and ii) a guide RNA. The guide RNA is in the form of a chimeric RNA which consists of the combination of a CRISPR (RNAcr) bacterial RNA and a RNAtracr (trans-activating RNA CRISPR) (Jinek et al., Science 2012). The guide RNA combines the targeting specificity of the RNAcr corresponding to the “spacing sequences” that serve as guides to the Cas proteins, and the conformational properties of the RNAtracr in a single transcript. When the guide RNA and the Cas protein are expressed simultaneously in the cell, the target genomic sequence can be permanently modified or interrupted. The modification is advantageously guided by a repair matrix. In general, the CRISPR system includes two main classes depending on the nuclease mechanism of action. Class 1 is made of multi-subunit effector complexes and includes type I, III and IV. Class 2 is made of single-unit effector modules, like Cas9 nuclease, and includes type II (II-A,II-B,II-C,II-C variant), V (V-A,V-B,V-C,V-D,V-E,V-U1,V-U2,V-U3,V-U4,V-U5) and VI (VI-A,VI-B1,VI-B2,VI-C,VI-D)
The sequence of interest according to the present disclosure comprises a nucleic acid sequence encoding Cas protein. A variety of CRISPR enzymes are available for use as a sequence of interest on the plasmid. In some embodiments, the CRISPR enzyme is a Type II CRISPR enzyme. In some embodiments, the CRISPR enzyme catalyzes DNA cleavage. In some other embodiments, the CRISPR enzyme catalyzes RNA cleavage. In one embodiment, the CRISPR enzymes may be coupled to a sgRNA. In certain embodiments, the sgRNA targets a gene selected in the group consisting of an antibiotic resistance gene, virulence protein or factor gene, toxin protein or factor gene, a bacterial receptor gene, a membrane protein gene, a structural protein gene, a secreted protein gene and a gene expressing resistance to a drug in general.
Non-limiting examples of Cas proteins as part of a multi-subunit effector or as a single-unit effector include Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cash, Cas7, Cas8, Cas9 (also known as Csn1 and Csx12), Cas10, Cas11 (SS), Cas12a (Cpf1), Cas12b (C2c1), Cas12c (C2c3), Cas12d (CasY), Cas12e (CasX), C2c4, C2c8, C2c5, C2c10, C2c9, Cas13a (C2c2), Cas13b (C2c6), Cas13c (C2c7), Cas13d, Csa5, Csc1, Csc2, Cse1, Cse2, Csy1, Csy2, Csy3, Csf1, Csf2, Csf3, Csf4, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csn2, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx13, Csx1, Csx15, SdCpf1, CmtCpf1, TsCpf1, CmaCpf1, PcCpf1, ErCpf1, FbCpf1, UbcCpf1, AsCpf1, LbCpf1, homologues thereof, orthologues thereof, variants thereof, or modified versions thereof. In some embodiments, the CRISPR enzyme cleaves both strands of the target nucleic acid at the Protospacer Adjacent Motif (PAM) site.
In a particular embodiment, the CRISPR enzyme is any Cas9 protein, for instance any naturally-occurring bacterial Cas9 as well as any variants, homologs or orthologs thereof.
By “Cas9” is meant a protein Cas9 (also called Csn1 or Csx12) or a functional protein, peptide or polypeptide fragment thereof, i.e. capable of interacting with the guide RNA(s) and of exerting the enzymatic activity (nuclease) which allows it to perform the double-strand cleavage of the DNA of the target genome. “Cas9” can thus denote a modified protein, for example truncated to remove domains of the protein that are not essential for the predefined functions of the protein, in particular the domains that are not necessary for interaction with the gRNA (s).
The sequence encoding Cas9 (the entire protein or a fragment thereof) as used in the context of the disclosure can be obtained from any known Cas9 protein (Fonfara et al., Nucleic Acids Res 42 (4), 2014; Koonin et al., Nat Rev Microbiol 15(3), 2017). Examples of Cas9 proteins useful in the present disclosure include, but are not limited to, Cas9 proteins of Streptococcus pyogenes (SpCas9), Streptococcus thermophiles (St1Cas9, St3Cas9), Streptococcus mutans, Staphylococcus aureus (SaCas9), Campylobacter jejuni (CjCas9), Francisella novicida (FnCas9) and Neisseria meningitides (NmCas9).
The sequence encoding Cpf1 (Cas12a) (the entire protein or a fragment thereof) as used in the context of the disclosure can be obtained from any known Cpf1 (Cas12a) protein (Koonin et al., 2017). Examples of Cpf1(Cas12a) proteins useful in the present disclosure include, but are not limited to, Cpf1(Cas12a) proteins of Acidaminococcus sp, Lachnospiraceae bacteriu and Francisella novicida.
The sequence encoding Cas13a (the entire protein or a fragment thereof) can be obtained from any known Cas13a (C2c2) protein (Abudayyeh et al., 2017). Examples of Cas13a (C2c2) proteins useful in the present disclosure include, but are not limited to, Cas13a (C2c2) proteins of Leptotrichia wadei (LwaCas13 a).
The sequence encoding Cas13d (the entire protein or a fragment thereof) can be obtained from any known Cas13d protein (Yan et al., 2018). Examples of Cas13d proteins useful in the present disclosure include, but are not limited to, Cas13d proteins of Eubacterium siraeum and Ruminococcus sp.
In a particular embodiment, the nucleic sequence of interest is a CRISPR/Cas9 system for the reduction of gene expression or inactivation a gene selected in the group consisting of an antibiotic resistance gene, virulence factor or protein gene, toxin factor or protein gene, a gene expressing a bacterial receptor, a membrane protein, a structural protein, a secreted protein, and a gene expressing resistance to a drug in general.
In one embodiment, the CRISPR system is used to target and inactivate a virulence factor. A virulence factor can be any substance produced by a pathogen that alter host-pathogen interaction by increasing the degree of damage done to the host. Virulence factors are used by pathogens in many ways, including, for example, in cell adhesion or colonization of a niche in the host, to evade the host's immune response, to facilitate entry to and egress from host cells, to obtain nutrition from the host, or to inhibit other physiological processes in the host. Virulence factors can include enzymes, endotoxins, adhesion factors, motility factors, factors involved in complement evasion, and factors that promote biofilm formation. For example, such targeted virulence factor gene can be E. coli virulence factor gene such as, without limitation, EHEC-HlyA, Stx1 (VT1), Stx2 (VT2), Stx2a (VT2a), Stx2b (VT2b), Stx2c (VT2c), Stx2d (VT2d), Stx2e (VT2e) and Stx2f (VT2f), Stx2h (VT2h), fimA, fimF, fimH, neuC, kpsE, sfa, foc, iroN, aer, iha, papC, papGI, papGII, papGIII, hlyC, cnfl, hra, sat, ireA, usp ompT, ibeA, malX, fyuA, irp2, traT, afaD, ipaH, eltB, estA, bfpA, eaeA, espA, aaiC, aatA, TEM, CTX, SHV, csgA, csgB, csgC, csgD, csgE, csgF, csgG, csgH, T1SS, T2SS, T3SS, T4SS, T5SS, T6SS (secretion systems). For example, such targeted virulence factor gene can be Shigella dysenteriae virulence factor gene such as, without limitation, stx1 and stx2. For example, such targeted virulence factor gene can be Yersinia pestis virulence factor gene such as, without limitation, yscF (plasmid-borne (pCD1) T3SS external needle subunit). For example, such targeted virulence factor gene can be Francisella tularensis virulence factor gene such as, without limitation, fs1A. For example, such targeted virulence factor gene can be Bacillus anthracis virulence factor gene such as, without limitation, pag (Anthrax toxin, cell-binding protective antigen). For example, such targeted virulence factor gene can be Vibrio cholera virulence factor gene such as, without limitation, ctxA and ctxB (cholera toxin), tcpA (toxin co-regulated pilus), and toxT (master virulence regulator). For example, such targeted virulence factor gene can be Pseudomonas aeruginosa virulence factor genes such as, without limitation, pyoverdine (e.g., sigma factor pvdS, biosynthetic genes pvdL, pvdl, pvdJ, pvdH, pvdA, pvdF, pvdQ, pvdN, pvdM, pvdO, pvdP, transporter genes pvdE, pvdR, pvdT, opmQ), siderophore pyochelin (e.g., pchD, pchC, pchB, pchA, pchE, pchF and pchG, and toxins (e.g., exoU, exoS and exoT). For example, such targeted virulence factor gene can be Klebsiella pneumoniae virulence factor genes such as, without limitation, fimA (adherence, type I fimbriae major subunit), and cps (capsular polysaccharide). For example, such targeted virulence factor gene can be Acinetobacter baumannii virulence factor genes such as, without limitation, ptk (capsule polymerization) and epsA (assembly). For example, such targeted virulence factor gene can be Salmonella enterica Typhi virulence factor genes such as, without limitation, MIA (invasion, SPI-1 regulator), ssrB (SPI-2 regulator), and those associated with bile tolerance, including efflux pump genes acrA, acrB and tolC. For example, such targeted virulence factor gene can be Fusobacterium nucleatum virulence factor genes such as, without limitation, FadA and TIGIT. For example, such targeted virulence factor gene can be Bacteroides fragilis virulence factor genes such as, without limitation, bft.
In another embodiment, the CRISPR/Cas9 system is used to target and inactivate an antibiotic resistance gene such as, without limitation, GyrB, ParE, ParY, AAC(1), AAC(2′), AAC(3), AAC(6′), ANT(2″), ANT(3″), ANT(4′), ANT(6), ANT(9), APH(2″), APH(3″), APH(3′), APH(4), APH(6), APH(7″), APH(9), ArmA, RmtA, RmtB, RmtC, Sgm, AER, BLA1, CTX-M, KPC, SHV, TEM, BlaB, CcrA, IMP, NDM, VIM, ACT, AmpC, CMY, LAT, PDC, OXA β-lactamase, mecA, Omp36, OmpF, PIB, bla (blaI, blaR1) and mec (mecl, mecR1) operons, Chloramphenicol acetyltransferase (CAT), Chloramphenicol phosphotransferase, Ethambutol-resistant arabinosyltransferase (EmbB), MupA, MupB, Integral membrane protein MprF, Cfr 23S rRNA methyltransferase, Rifampin ADP-ribosyltransferase (Arr), Rifampin glycosyltransferase, Rifampin monooxygenase, Rifampin phosphotransferase, DnaA, RbpA, Rifampin-resistant beta-subunit of RNA polymerase (RpoB), Erm 23S rRNA methyltransferases, Lsa, MsrA, Vga, VgaB, Streptogramin Vgb lyase, Vat acetyltransferase, Fluoroquinolone acetyltransferase, Fluoroquinolone-resistant DNA topoisomerases, Fluoroquinolone-resistant GyrA, GyrB, ParC, Quinolone resistance protein (Qnr), FomA, FomB, FosC, FosA, FosB, FosX, VanA, VanB, VanD, VanR, VanS, Lincosamide nucleotidyltransferase (Lin), EreA, EreB, GimA, Mgt, Ole, Macrolide phosphotransferases (MPH), MefA, MefE, Mel, Streptothricin acetyltransferase (sat), Sul1, Sul2, Sul3, sulfonamide-resistant FolP, Tetracycline inactivation enzyme TetX, TetA, TetB, TetC, Tet30, Tet31, TetM, TetO, TetQ, Tet32, Tet36, MacAB-TolC, MsbA, MsrA, VgaB, EmrD, EmrAB-TolC, NorB, GepA, MepA, AdeABC, AcrD, MexAB-OprM, mtrCDE, EmrE, adeR, acrR, baeSR, mexR, phoPQ, mtrR, or any antibiotic resistance gene described in the Comprehensive Antibiotic Resistance Database (CARD https://card.mcmaster.ca/).
In another embodiment, the CRISPR/Cas9 system is used to target and inactivate a bacterial toxin gene. Bacterial toxin can be classified as either exotoxins or endotoxins. Exotoxins are generated and actively secreted; endotoxins remain part of the bacteria. The response to a bacterial toxin can involve severe inflammation and can lead to sepsis. Such toxin can be for example Botulinum neurotoxin, Tetanus toxin, Staphylococus toxins, Diphteria toxin, Anthrax toxin, Alpha toxin, Pertussis toxin, Shiga toxin, Heat-stable enterotoxin (E. coli ST), colibactin, BFT (B. fragilis toxin) or any toxin described in Henkel et al., (Toxins from Bacteria in EXS. 2010; 100: 1-29).
The bacteria targeted by bacterial delivery vehicles disclosed herein can be any bacteria present in a mammal organism. In a certain aspect, the bacteria are targeted through interaction of the chimeric RBPs expressed by the delivery vehicles with the bacterial cell. It can be any commensal, symbiotic or pathogenic bacteria of the microbiota or microbiome.
A microbiome may comprise of a variety of endogenous bacterial species, any of which may be targeted in accordance with the present disclosure. In some embodiments, the genus and/or species of targeted endogenous bacterial cells may depend on the type of bacteriophages being used for preparing the bacterial delivery vehicles. For example, some bacteriophages exhibit tropism for, or preferentially target, specific host species of bacteria. Other bacteriophages do not exhibit such tropism and may be used to target a number of different genus and/or species of endogenous bacterial cells.
Examples of bacterial cells include, without limitation, cells from bacteria of the genus Yersinia spp., Escherichia spp., Klebsiella spp., Acinetobacter spp., Bordetella spp., Neisseria spp., Aeromonas spp., Franciesella spp., Corynebacterium spp., Citrobacter spp., Chlamydia spp., Hemophilus spp., Brucella spp., Mycobacterium spp., Legionella spp., Rhodococcus spp., Pseudomonas spp., Helicobacter spp., Vibrio spp., Bacillus spp., Erysipelothrix spp., Salmonella spp., Streptomyces spp., Streptococcus spp., Staphylococcus spp., Bacteroides spp., Prevotella spp., Clostridium spp., Bifidobacterium spp., Clostridium spp., Brevibacterium spp., Lactococcus spp., Leuconostoc spp., Actinobacillus spp., Selnomonas spp., Shigella spp., Zymonas spp., Mycoplasma spp., Treponema spp., Leuconostoc spp., Corynebacterium spp., Enterococcus spp., Enterobacter spp., Pyrococcus spp., Serratia spp., Morganella spp., Parvimonas spp., Fusobacterium spp., Actinomyces spp., Porphyromonas spp., Micrococcus spp., Bartonella spp., Borrelia spp., Brucelia spp., Campylobacter spp., Chlamydophilia spp., Cutibacterium spp., Propionibacterium spp., Gardnerella spp., Ehrlichia spp., Haemophilus spp., Leptospira spp., Listeria spp., Mycoplasma spp., Nocardia spp., Rickettsia spp., Ureaplasma spp., and Lactobacillus spp, and a mixture thereof.
Thus, bacterial delivery vehicles may target (e.g., specifically target) a bacterial cell from any one or more of the foregoing genus of bacteria to specifically deliver the payload of interest according to the disclosure.
Preferably, the targeted bacteria can be selected from the group consisting of Yersinia spp., Escherichia spp., Klebsiella spp., Acinetobacter spp., Pseudomonas spp., Helicobacter spp., Vibrio spp, Salmonella spp., Streptococcus spp., Staphylococcus spp., Bacteroides spp., Clostridium spp., Shigella spp., Enterococcus spp., Enterobacter spp., Listeria spp., Cutibacterium spp., Propionibacterium spp., Fusobacterium spp., Porphyromonas spp. and Gardnerella spp.
In some embodiments, bacterial cells of the present disclosure are anaerobic bacterial cells (e.g., cells that do not require oxygen for growth). Anaerobic bacterial cells include facultative anaerobic cells such as but not limited to Escherichia coli, Shewanella oneidensis, Gardnerella vaginalis and Listeria. Anaerobic bacterial cells also include obligate anaerobic cells such as, for example, Bacteroides, Clostridium, Cutibacterium, Propionibacterium, Fusobacterium and Porphyromona species. In humans, anaerobic bacteria are most commonly found in the gastrointestinal tract. In some particular embodiment, the targeted bacteria are thus bacteria most commonly found in the gastrointestinal tract. Bacteriophages used for preparing the bacterial virus particles, and then the bacterial virus particles, may target (e.g., to specifically target) anaerobic bacterial cells according to their specific spectra known by the person skilled in the art to specifically deliver the plasmid.
In some embodiments, the targeted bacterial cells are, without limitation, Bacteroides thetaiotaomicron, Bacteroides fragilis, Bacteroides distasonis, Bacteroides vulgatus, Clostridium leptum, Clostridium coccoides, Staphylococcus aureus, Bacillus subtilis, Clostridium butyricum, Brevibacterium lactofermentum, Streptococcus agalactiae, Lactococcus lactis, Leuconostoc lactis, Actinobacillus actinobycetemcomitans, cyanobacteria, Escherichia coli, Helicobacter pylori, Selnomonas ruminatium, Shigella sonnei, Zymomonas mobilis, Mycoplasma mycoides, Treponema denticola, Bacillus thuringiensis, Staphilococcus lugdunensis, Leuconostoc oenos, Corynebacterium xerosis, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus acidophilus, Enterococcus faecalis, Bacillus coagulans, Bacillus cereus, Bacillus popillae, Synechocystis strain PCC6803, Bacillus liquefaciens, Pyrococcus abyssi, Selenomonas nominantium, Lactobacillus hilgardii, Streptococcus ferus, Lactobacillus pentosus, Bacteroides fragilis, Staphylococcus epidermidis, Streptomyces phaechromogenes, Streptomyces ghanaenis, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Morganella morganii, Citrobacter freundii, Propionibacterium freudenreichii, Pseudomonas aerigunosa, Parvimonas micra, Prevotella intermedia, Fusobacterium nucleatum, Prevotella nigrescens, Actinomyces israelii, Porphyromonas endodontalis, Porphyromonas gingivalis Micrococcus luteus, Bacillus megaterium, Aeromonas hydrophila, Aeromonas caviae, Bacillus anthracis, Bartonella henselae, Bartonella Quintana, Bordetella pertussis, Borrelia burgdorferi, Borrelia garinii, Borrelia afzelii, Borrelia recurrentis, Brucella abortus, Brucella canis, Brucella melitensis, Brucella suis, Campylobacter jejuni, Campylobacter coli, Campylobacter fetus, Chlamydia pneumoniae, Chlamydia trachomatis, Chlamydophila psittaci, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheria, Cutibacterium acnes (formerly Propionibacterium acnes), Ehrlichia canis, Ehrlichia chaffeensis, Enterococcus faecium, Francisella tularensis, Haemophilus influenza, Legionella pneumophila, Leptospira interrogans, Leptospira santarosai, Leptospira weilii, Leptospira noguchii, Listeria monocytogenes, Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycoplasma pneumonia, Neisseria gonorrhoeae, Neisseria meningitides, Nocardia asteroids, Rickettsia rickettsia, Salmonella enteritidis, Salmonella typhi, Salmonella paratyphi, Salmonella typhimurium, Shigella flexnerii, Shigella dysenteriae, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes, Gardnerella vaginalis, Streptococcus viridans, Treponema pallidum, Ureaplasma urealyticum, Vibrio cholera, Vibrio parahaemolyticus, Yersinia pestis, Yersinia enterocolitica, Yersinia pseudotuberculosis, Actinobacter baumanii, Pseudomonas aerigunosa, and a mixture thereof, preferably the bacteria of interest are selected from the group consisting of Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, Enterobacter cloacae, and Enterobacter aerogenes, and a mixture thereof.
In one embodiment, the targeted bacteria are Escherichia coli.
Thus, bacteriophages used for preparing the bacterial delivery vehicles, and then the bacterial delivery vehicles, may target (e.g., specifically target) a bacterial cell from any one or more of the foregoing genus and/or species of bacteria to specifically deliver the plasmid.
In one embodiment, the targeted bacteria are pathogenic bacteria. The targeted bacteria can be virulent bacteria.
The targeted bacteria can be antibacterial resistance bacteria, preferably selected from the group consisting of extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli, ESBL Klebsiella pneumoniae, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant (MDR) Acinetobacter baumannii, MDR Enterobacter spp., and a combination thereof. Preferably, the targeted bacteria can be selected from the group consisting of extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli strains.
Alternatively, the targeted bacterium can be a bacterium of the microbiome of a given species, preferably a bacterium of the human microbiota.
The present disclosure is directed to bacterial delivery vehicle containing the payload as described herein. The bacterial delivery vehicles are prepared from bacterial virus. The bacterial delivery vehicles are chosen in order to be able to introduce the payload into the targeted bacteria.
Bacterial viruses, from which the bacterial delivery vehicles having chimeric receptor binding proteins may be derived, are preferably bacteriophages. Optionally, the bacteriophage is selected from the Order Caudovirales consisting of, based on the taxonomy of Krupovic et al, Arch Virol, 2015:
Bacteriophages may be selected from the family Myoviridae (such as, without limitation, genus Cp220virus, Cplvirus, Ea214virus, Felixolvirus, Mooglevirus, Suspvirus, Hp1virus, P2virus, Kayvirus, P100virus, Silviavirus, Spolvirus, Tsarbombavirus, Twortvirus, Cc31virus, Jd18virus, Js98virus, Kp15virus, Moonvirus, Rb49virus, Rb69virus, S16virus, Schizot4virus, Sp18virus, T4virus, Cr3virus, Selvirus, V5virus, Abouovirus, Agatevirus, Agrican357virus, Ap22virus, Arvlvirus, B4virus, Bastillevirus, Bc431virus, Bcep78virus, Bcepmuvirus, Biquartavirus, Bxz1virus, Cd119virus, Cp51virus, Cvm10virus, Eah2virus, Elvirus, Hapunavirus, Jimmervirus, Kpp10virus, M12virus, Machinavirus, Marthavirus, Msw3virus, Muvirus, Myohalovirus, Nit1virus, P1virus, Pakpunavirus, Pbunavirus, Phikzvirus, Rheph4virus, Rsl2virus, Rslunavirus, Secunda5virus, Seplvirus, Spn3virus, Svunavirus, Tglvirus, Vhmlvirus and Wphvirus)
Bacteriophages may be selected from the family Podoviridae (such as, without limitation, genus Fri1virus, Kp32virus, Kp34virus, Phikmvvirus, Pradovirus, Sp6virus, T7virus, Cp1virus, P68virus, Phi29virus, Nona33virus, Pocjvirus, Tl2011virus, Bcep22virus, Bpplvirus, Cba41virus, Dfl12virus, Ea92virus, Epsilon15virus, F116virus, G7cvirus, Jwalphavirus, Kflvirus, Kpp25virus, Lit1virus, Luz24virus, Luz7virus, N4virus, Nonanavirus, P22virus, Pagevirus, Phieco32virus, Prtbvirus, Sp58virus, Una961virus and Vp5virus)
    • Bacteriophages may be selected from the family Siphoviridae (such as, without limitation, genus Camvirus, Likavirus, R4virus, Acadianvirus, Coopervirus, Pglvirus, Pipefishvirus, Rosebushvirus, Brujitavirus, Che9cvirus, Hawkeyevirus, Plotvirus, Jerseyvirus, K1gvirus, Sp3 lvirus, Lmd1virus, Una4virus, Bongovirus, Reyvirus, Buttersvirus, Charlievirus, Redivirus, Baxtervirus, Nymphadoravirus, Bignuzvirus, Fishburnevirus, Phayoncevirus, Kp36virus, Rogue1virus, Rtpvirus, T1virus, Tlsvirus, Ab18virus, Amigovirus, Anatolevirus, Andromedavirus, Attisvirus, Barnyardvirus, Bernal13virus, Biseptimavirus, Bronvirus, C2virus, C5virus, Cba181virus, Cbastvirus, Cecivirus, Che8virus, Chivirus, Cjw1virus, Corndogvirus, Cronusvirus, D3112virus, D3virus, Decurrovirus, Demosthenesvirus, Doucettevirus, E125virus, Eiauvirus, Ff47virus, Gaiavirus, Gilesvirus, Gordonvirus, Gordtnkvirus, Harrisonvirus, Hk578virus, Hk97virus, Jenstvirus, Jwxvirus, Kelleziovirus, Korravirus, L5virus, lambdavirus, Laroyevirus, Liefievirus, Marvinvirus, Mudcatvirus, N15virus, Nonagvirus, Np1virus, Omegavirus, P12002virus, P12024virus, P23virus, P70virus, Pa6virus, Pamx74virus, Patiencevirus, Pbi1virus, Pepy6virus, Pfr1virus, Phic31virus, Phicbkvirus, Phietavirus, Phifelvirus, Phijl1virus, Pis4avirus, Psavirus, Psimunavirus, Rdjlvirus, Rer2virus, Sap6virus, Send513virus, Septima3virus, Seuratvirus, Sextaecvirus, Sfi11virus, Sfi21dtivirus, Sitaravirus, Sk1virus, Slashvirus, Smoothievirus, Soupsvirus, Spbetavirus, Ssp2virus, T5virus, Tankvirus, Tin2virus, Titanvirus, Tm4virus, Tp2lvirus, Tp84virus, Triavirus, Trigintaduovirus, Vegasvirus, Vendettavirus, Wbetavirus, Wildcatvirus, Wizardvirus, Woesvirus, Xp10virus, Ydn12virus and Yuavirus)
Bacteriophages may be selected from the family Ackermannviridae (such as, without limitation, genus Ag3virus, Limestonevirus, Cba120virus and Vi1virus)
Optionally, the bacteriophage is not part of the order Caudovirales but from families with unassigned order such as, without limitation, family Tectiviridae (such as genus Alphatectivirus, Betatectivirus), family Corticoviridae (such as genus Corticovirus), family Inoviridae (such as genus Fibrovirus, Habenivirus, Inovirus, Lineavirus, Plectrovirus, Saetivirus, Vespertiliovirus), family Cystoviridae(such as genus Cystovirus), family Leviviridae(such as genus Allolevivirus, Levivirus), family Microviridae (such as genus Alpha3microvirus, G4microvirus, Phix174microvirus, Bdellomicrovirus, Chlamydiamicrovirus, Spiromicrovirus) and family Plasmaviridae (such as genus Plasmavirus).
Optionally, the bacteriophage is targeting Archea not part of the Order Caudovirales but from families with Unassigned order such as, without limitation, Ampullaviridae, FuselloViridae, Globuloviridae, Guttaviridae, Lipothrixviridae, Pleolipoviridae, Rudiviridae, Salterprovirus and Bicaudaviridae.
A non-exhaustive listing of bacterial genera and their known host-specific bacteria viruses is presented in the following paragraphs. The chimeric RBPs and the bacterial delivery vehicles disclosed herein may be engineered, as non-limiting examples, from the following phages. Synonyms and spelling variants are indicated in parentheses. Homonyms are repeated as often as they occur (e.g., D, D, d). Unnamed phages are indicated by “NN” beside their genus and their numbers are given in parentheses.
Bacteria of the genus Actinomyces can be infected by the following phages: Av-I, Av-2, Av-3, BF307, CT1, CT2, CT3, CT4, CT6, CT7, CT8 and 1281.
Bacteria of the genus Aeromonas can be infected by the following phages: AA-I, Aeh2, N, PM1, TP446, 3, 4, 11, 13, 29, 31, 32, 37, 43, 43-10T, 51, 54, 55R.1, 56, 56RR2, 57, 58, 59.1, 60, 63, Aeh1, F, PM2, 1, 25, 31, 40RR2.8t, (syn=44R), (syn=44RR2.8t), 65, PM3, PM4, PM5 and PM6.
Bacteria of the genus Bacillus can be infected by the following phages: A, aizl, Al—K—I, B, BCJA1, BC1, BC2, BLL1, BL1, BP142, BSL1, BSL2, BS1, BS3, BS8, BS15, BS18, BS22, BS26, BS28, BS31, BS104, BS105, BS106, BTB, B1715V1, C, CK-I, Coll, Corl, CP-53, CS-I, CSi, D, D, D, D5, entl, FP8, FP9, FSi, FS2, FS3, FS5, FS8, FS9, G, GH8, GT8, GV-I, GV-2, GT-4, g3, g12, g13, g14, g16, g17, g21, g23, g24, g29, H2, kenl, KK-88, Kuml, Kyul, J7W-1, LP52, (syn=LP-52), L7, Mexl, MJ-I, mor2, MP-7, MPlO, MP12, MP14, MP15, Neol, N°2, N5, N6P, PBC1, PBLA, PBP1, P2, S-a, SF2, SF6, Shal, Sill, SP02, (syn=ΦSPP1), SPβ, STI, STi, SU-Il, t, TbI, Tb2, Tb5, TbIO, Tb26, Tb51, Tb53, Tb55, Tb77, Tb97, Tb99, Tb560, Tb595, Td8, Td6, Td15, TgI, Tg4, Tg6, Tg7, Tg9, TgIO, TgIl, Tg13, Tg15, Tg21, Tin1, Tin7, Tin8, Tin13, Tm3, Tocl, Togl, toll, TP-I, TP-10vir, TP-15c, TP-16c, TP-17c, TP-19, TP35, TP51, TP-84, Tt4, Tt6, type A, type B, type C, type D, type E, Tφ3, VA-9, W, wx23, wx26, Yunl, α, γ, pl 1, φmed-2, φT, φμ-4, φ75, φlO5, (syn=φlO5), IA, IB, 1-97A, 1-97B, 2, 2, 3, 3, 3, 5, 12, 14, 20, 30, 35, 36, 37, 38, 41C, 51, 63, 64, 138D, I, II, IV, NN-Bacillus (13), alel, AR1, AR2, AR3, AR7, AR9, Bace-11, (syn=11), Bastille, BL1, BL2, BL3, BL4, BLS, BL6, BL8, BL9, BP124, BS28, BS80, Ch, CP-51, CP-54, D-5, darl, denl, DP-7, entl, FoSi, FoS2, FS4, FS6, FS7, G, gall, gamma, GE1, GF-2, GSi, GT-I, GT-2, GT-3, GT-4, GT-5, GT-6, GT-7, GV-6, g15, 19, 110, ISi, K, MP9, MP13, MP21, MP23, MP24, MP28, MP29, MP30, MP32, MP34, MP36, MP37, MP39, MP40, MP41, MP43, MP44, MP45, MP47, MP50, NLP-I, No. 1, N17, N19, PBS1, PK1, PMB1, PMB12, PMJ1, S, SPO1, SP3, SP5, SP6, SP7, SP8, SP9, SPlO, SP-15, SP50, (syn=SP-50), SP82, SST, subl, SW, Tg8, Tg12, Tg13, Tg14, thul, thuΛ, thuS, Tin4, Tin23, TP-13, TP33, TP50, TSP-I, type V, type VI, V, Vx, β22, φe, φNR2, φ25, φ63, 1, 1, 2, 2C, 3NT, 4, 5, 6, 7, 8, 9, 10, 12, 12, 17, 18, 19, 21, 138, III, 4 (B. megateriwn), 4 (B. sphaericus), AR13, BPP-IO, BS32, BS107, B1, B2, GA-I, GP-IO, GV-3, GV-5, g8, MP20, MP27, MP49, Nf, PP5, PP6, SF5, Tg18, TP-I, Versailles, φl5, φ29, 1-97, 837/IV, mï-Bacillus (1), BatlO, BSLlO, BSLI1, BS6, BSI1, BS16, BS23, BSlOl, BS102, g18, mor1, PBL1, SN45, thu2, thu3, TmI, Tm2, TP-20, TP21, TP52, type F, type G, type IV, HN-BacMus (3), BLE, (syn=θc), BS2, BS4, BS5, BS7, BlO, B12, BS20, BS21, F, MJ-4, PBA12, AP50, AP50-04, AP50-11, AP50-23, AP50-26, AP50-27 and Bam35. The following Bacillus-specific phages are defective: DLP10716, DLP-11946, DPB5, DPB12, DPB21, DPB22, DPB23, GA-2, M, No. IM, PBLB, PBSH, PBSV, PBSW, PBSX, PBSY, PBSZ, phi, SPa, type 1 and μ.
Bacteria of the genus Bacteriodes can be infected by the following phages: ad I2, Baf-44, Baf-48B, Baf-64, Bf-I, Bf-52, B40-8, F1, β1, φA1, φBrO1, φBrO2, 11, 67.1, 67.3, 68.1, mt-Bacteroides (3), Bf42, Bf71, HN-Bdellovibrio (1) and BF-41.
Bacteria of the genus Bordetella can be infected by the following phages: 134 and NN-Bordetella (3).
Bacteria of the genus Borrellia can be infected by the following phages: NN-Borrelia (1) and NN-Borrelia (2).
Bacteria of the genus Brucella can be infected by the following phages: A422, Bk, (syn=Berkeley), BM29, FOi, (syn=FO1), (syn=FQ1), D, FP2, (syn=FP2), (syn=FD2), Fz, (syn=Fz75/13), (syn=Firenze 75/13), (syn=Fi), Fi, (syn=Fl), Fim, (syn=FIm), (syn=Fim), FiU, (syn=FlU), (syn=FiU), F2, (syn=F2), F3, (syn=F3), F4, (syn=F4), F5, (syn=F5), F6, F7, (syn=F7), F25, (syn=F25), (syn=£25), F25U, (syn=F25u), (syn=F25U), (syn=F25V), F44, (syn-F44), F45, (syn=F45), F48, (syn=F48), I, Im, M, MC/75, M51, (syn=M85), P, (syn=D), S708, R, Tb, (syn=TB), (syn=Tbilisi), W, (syn=Wb), (syn=Weybridge), X, 3, 6, 7, 10/1, (syn=10), (syn=F8), (syn=F8), 12m, 24/11, (syn=24), (syn=F9), (syn=F9), 45/111, (syn=45), 75, 84, 212/XV, (syn=212), (syn=Fi0), (syn=FlO), 371/XXIX, (syn=371), (syn=Fn), (syn=Fl 1) and 513.
Bacteria of the genus Burkholderia can be infected by the following phages: CP75, NN-Burkholderia (1) and 42.
Bacteria of the genus Campylobacter can be infected by the following phages: C type, NTCC12669, NTCC12670, NTCC12671, NTCC12672, NTCC12673, NTCC12674, NTCC12675, NTCC12676, NTCC12677, NTCC12678, NTCC12679, NTCC12680, NTCC12681, NTCC12682, NTCC12683, NTCC12684, 32f, 111c, 191, NN-Campylobacter (2), Vfi-6, (syn=V19), VfV-3, V2, V3, V8, V16, (syn=Vfi-1), V19, V20(V45), V45, (syn=V-45) and NN-Campylobacter (1).
Bacteria of the genus Chlamydia can be infected by the following phage: Chpl.
Bacteria of the genus Clostridium can be infected by the following phages: CAK1, CA5, Ca7, CEβ, (syn=1C), CEγ, Cldl, c-n71, c-203 Tox-, DEβ, (syn=ID), (syn=lDt0X+), HM3, KM1, KT, Ms, NA1, (syn=Naltox+), PA135Oe, Pfó, PL73, PL78, PL81, Pl, P50, P5771, P19402, 1Ct0X+, 2Ct0X\ 2D3 (syn=2Dt0X+), 3C, (syn=3Ctox+), 4C, (syn=4Ct0X+), 56, III-1, NN-Clostridium (61), NBlt0X+, α1, CA1, HMT, HM2, PF15 P-23, P-46, Q-05, Q-oe, Q-16, Q-21, Q-26, Q-40, Q-46, S111, SA02, WA01, WA03, Wm, W523, 80, C, CA2, CA3, CPT1, CPT4, cl, c4, c5, HM7, H11/A1, H18/Ax, FWS23, Hi58ZA1, K2ZA1, K21ZS23, ML, NA2t0X; Pf2, Pf3, Pf4, S9ZS3, S41ZA1, S44ZS23, α2, 41, 112ZS23, 214/S23, 233/Ai, 234/S23, 235/S23, II-1, II-2, II-3, NN-Clostridium (12), CA1, F1, K, S2, 1, 5 and NN-Clostridium (8).
Bacteria of the genus Corynebacterium can be infected by the following phages: CGK1 (defective), A, A2, A3, A1O1, A128, A133, A137, A139, A155, A182, B, BF, B17, B18, B51, B271, B275, B276, B277, B279, B282, C, capi, CC1, CG1, CG2, CG33, CL31, Cog, (syn=CG5), D, E, F, H, H-I, hqi, hq2, 11ZH33, Ii/31, J, K, K, (syn=Ktox″), L, L, (syn=Ltox+), M, MC-I, MC-2, MC-3, MC-4, MLMa, N, O, ovi, ov2, ov3, P, P, R, RP6, RS29, S, T, U, UB1, ub2, UH1, UH3, uh3, uh5, uh6, β, (syn=βtox+), βhv64, βvir, γ, (syn=γtoχ−), γl9, δ, (syn=δ′ox+), p, (syn=ptoχ−), Φ9, φ984, ω, IA, 1/1180, 2, 2/1180, 5/1180, 5ad/9717, 7/4465, 8/4465, 8ad/10269, 10/9253, 13Z9253, 15/3148, 21/9253, 28, 29, 55, 2747, 2893, 4498 and 5848.
Bacteria of the genus Enterococcus are infected by the following phage: DF78, F1, F2, 1, 2, 4, 14, 41, 867, Dl, SB24, 2BV, 182, 225, C2, C2F, E3, E62, DS96, H24, M35, P3, P9, SB1O1, S2, 2BII, 5, 182a, 705, 873, 881, 940, 1051, 1057, 21096C, NN-Enterococcus (1), PE1, F1, F3, F4, VD13, 1, 200, 235 and 341.
Bacteria of the genus Erysipelothrix can be infected by the following phage: NN-Eiysipelothrix (1).
Bacteria of the genus Escherichia can be infected by the following phages: BW73, B278, D6, D108, E, E1, E24, E41, FI-2, FI-4, FI-5, HI8A, Ffl8B, i, MM, Mu, (syn=mu), (syn=MuI), (syn=Mu-I), (syn=MU-I), (syn=MuI), (syn=μ), 025, PhI-5, Pk, PSP3, P1, P1D, P2, P4 (defective), Sl, Wφ, φK13, φR73 (defective), φ1, φ2, φ7, φ92, ψ (defective), 7 A, 8φ, 9φ, 15 (defective), 18, 28-1, 186, 299, HH-Escherichia (2), AB48, CM, C4, C16, DD-VI, (syn=Dd-Vi), (syn=DDVI), (syn=DDVi), E4, E7, E28, FIl, FI3, H, H1, H3, H8, K3, M, N, ND-2, ND-3, ND4, ND-5, ND6, ND-7, Ox-I (syn=OX1), (syn=HF), Ox-2 (syn=0x2), (syn=0X2), Ox-3, Ox-4, Ox-5, (syn=0X5), Ox-6, (syn=66F), (syn=φ66t), (syn=φ66t-)5 0111, PhI-I, RB42, RB43, RB49, RB69, S, SaI-I, Sal-2, Sal-3, Sal-4, Sal-5, Sal-6, TC23, TC45, TuII*-6, (syn=TuII*), TuIP-24, TuII*46, TuIP-60, T2, (syn=ganuTia), (syn=γ), (syn=PC), (syn=P.C.), (syn=T-2), (syn=T2), (syn=P4), T4, (syn=T-4), (syn=T4), T6, T35, α1, 1, IA, 3, (syn=Ac3), 3A, 3T+, (syn=3), (syn=Ml), 5φ, (syn=φ5), 9266Q, CFO103, HK620, J, K, KlF, m59, no. A, no. E, no. 3, no. 9, N4, sd, (syn=Sd), (syn=SD), (syn=Sa)3 (syn=sd), (syn=SD), (syn=CD), T3, (syn=T-3), (syn=T3), T7, (syn=T-7), (syn=T7), WPK, W31, ΔH, φC3888, φK3, φK7, φK12, φV-1, Φ04-CF, Φ05, Φ06, Φ07, φ1, φ1.2, φ20, φ95, φ263, φ1O92, φ1, φ11, (syn=φW), Ω8, 1, 3, 7, 8, 26, 27, 28-2, 29, 30, 31, 32, 38, 39, 42, 933W, NN-Escherichia (1), Esc-7-11, AC30, CVX-5, C1, DDUP, EC1, EC2, E21, E29, F1, F26S, F27S, Hi, HK022, HK97, (syn=ΦHK97), HK139, HK253, HK256, K7, ND-I, no.D, PA-2, q, S2, Tl, (syn=α), (syn=P28), (syn=T-I), (syn=Tx), T3C, T5, (syn=T-5), (syn=T5), UC-I, w, β4, γ2, λ (syn=lambda), (syn=Φλ), ΦD326, φγ, Φ06, Φ7, Φ10, φ80, χ, (syn=χi), (syn=φχ), (syn=φχi), 2, 4, 4A, 6, 8A, 102, 150, 168, 174, 3000, AC6, AC7, AC28, AC43, AC50, AC57, AC81, AC95, HK243, K1O, ZG/3A, 5, 5A, 21EL, H19-J and 933H.
Bacteria of the genus Fusobacterium are infected by the following phage: NN-Fusobacterium (2), fv83-554/3, fv88-531/2, 227, fv2377, fv2527 and fv8501.
Bacteria of the genus Haemophilus are infected by the following phage: HP1, S2 and N3.
Bacteria of the genus Helicobacter are infected by the following phage: HP1 and {circumflex over ( )}{circumflex over ( )}-Helicobacter (1).
Bacteria of the genus Klebsiella are infected by the following phage: AIO-2, KI4B, Kl6B, Kl9, (syn=Kl9), Kl14, Kl15, Kl21, Kl28, Kl29, KI32, Kl33, Kl35, Kl106B, Kl171B, Kl181B, Kl832B, AIO-I, AO-I, AO-2, AO-3, FC3-10, K, Kl1, (syn=KIl), Kl2, (syn=K12), Kl3, (syn=K13), (syn=Kl 70/11), Kl4, (syn=K14), Kl5, (syn=K15), Kl6, (syn=K16), Kl7, (syn=K17), Kl8, (syn=K18), Kl19, (syn=K19), Kl27, (syn=K127), Kl31, (syn=K131), Kl35, Kl171B, II, VI, IX, CI-I, Kl4B, Kl8, Kl11, Kl12, Kl13, Kl16, Kl17, Kl18, Kl20, Kl22, Kl23, Kl24, Kl26, Kl30, Kl34, Kl106B, KIi65B, Kl328B, KLXI, K328, P5046, 11, 380, III, IV, VII, VIII, FC3-11, Kl2B, (syn=K12B), Kl25, (syn=K125), Kl42B, (syn=K142), (syn=K142B), Kl181B, (syn=KIl 81), (syn=K1181B), Kl765/ !, (syn=K1765/1), Kl842B, (syn=K1832B), Kl937B, (syn=K1937B), Ll, φ28, 7, 231, 483, 490, 632 and 864/100.
Bacteria of the genus Lepitospira are infected by the following phage: LEl, LE3, LE4 and ˜NN-Leptospira (1).
Bacteria of the genus Listeria are infected by the following phage: A511, 01761, 4211, 4286, (syn=BO54), A005, A006, A020, A500, A502, A511, Al 18, A620, A640, B012, B021, B024, B025, B035, B051, B053, B054, B055, B056, BlOl, BIlO, B545, B604, B653, C707, D441, HSO47, HlOG, H8/73, H19, H21, H43, H46, H107, H108, HI lO, H163/84, H312, H340, H387, H391/73, H684/74, H924A, PSA, U153, φMLUP5, (syn=P35), 00241, 00611, 02971A, 02971C, 5/476, 5/911, 5/939, 5/11302, 5/11605, 5/11704, 184, 575, 633, 699/694, 744, 900, 1090, 1317, 1444, 1652, 1806, 1807, 1921/959, 1921/11367, 1921/11500, 1921/11566, 1921/12460, 1921/12582, 1967, 2389, 2425, 2671, 2685, 3274, 3550, 3551, 3552, 4276, 4277, 4292, 4477, 5337, 5348/11363, 5348/11646, 5348/12430, 5348/12434, 10072, 11355C, 11711A, 12029, 12981, 13441, 90666, 90816, 93253, 907515, 910716 and NN-Lisferia (15).
Bacteria of the genus Morganella are infected by the following phage: 47.
Bacteria of the genus Mycobacterium are infected by the following phage: 13, AGl, ALi, ATCC 11759, A2, B.C3, BG2, BK1, BK5, butyricum, B-I, B5, B7, B30, B35, Clark, Cl, C2, DNAIII, DSP1, D4, D29, GS4E, (syn=GS4E), GS7, (syn=GS-7), (syn=GS7), IPa, lacticola, Legendre, Leo, L5, (syn=ΦL-5), MC-I, MC-3, MC-4, minetti, MTPHI l, Mx4, MyF3P/59a, phlei, (syn=phlei 1), phlei 4, Polonus II, rabinovitschi, smegmatis, TM4, TM9, TMlO, TM20, Y7, YlO, φ630, IB, IF, IH, 1/1, 67, 106, 1430, Bl, (syn=Bol), B24, D, D29, F-K, F-S, HP, Polonus I, Roy, Rl, (syn=Rl-Myb), (syn=Ri), 11, 31, 40, 50, 103a, 103b, 128, 3111-D, 3215-D and NN-Mycobacterium (1).
Bacteria of the genus Neisseria are infected by the following phage: Group I, group II and NPl.
Bacteria of the genus Nocardia are infected by the following phage: MNP8, NJ-L, NS-8, N5 and TtiN-Nocardia.
Bacteria of the genus Proteus are infected by the following phage: Pm5, 13vir, 2/44, 4/545, 6/1004, 13/807, 20/826, 57, 67b, 78, 107/69, 121, 9/0, 22/608, 30/680, PmI, Pm3, Pm4, Pm6, Pm7, Pm9, PmIO, PmI l, Pv2, πl, φm, 7/549, 9B/2, 10A/31, 12/55, 14, 15, 16/789, 17/971, 19A/653, 23/532, 25/909, 26/219, 27/953, 32A/909, 33/971, 34/13, 65, 5006M, 7480b, VI, 13/3a, Clichy 12, π2600, φχ7, 1/1004, 5/742, 9, 12, 14, 22, 24/860, 2600/D52, Pm8 and 24/2514.
Bacteria of the genus Providencia are infected by the following phage: PL25, PL26, PL37, 9211/9295, 9213/921 Ib, 9248, 7/R49, 7476/322, 7478/325, 7479, 7480, 9000/9402 and 9213/921 Ia.
Bacteria of the genus Pseudomonas are infected by the following phage: PfI, (syn=Pf-I), Pf2, Pf3, PP7, PRRl, 7s, im-Pseudomonas (1), AI-I, AI-2, B 17, B89, CB3, Col 2, Col 11, Col 18, Col 21, C154, C163, C167, C2121, E79, F8, ga, gb, H22, K1, M4, N2, Nu, PB-I, (syn=PBl), pfl6, PMN17, PPl, PP8, Psal, PsPl, PsP2, PsP3, PsP4, PsP5, PS3, PS17, PTB80, PX4, PX7, PYOl, PYO2, PYO5, PYO6, PYO9, PYOlO, PYO13, PYO14, PYO16, PYO18, PYO19, PYO20, PYO29, PYO32, PYO33, PYO35, PYO36, PYO37, PYO38, PYO39, PYO41, PYO42, PYO45, PYO47, PYO48, PYO64, PYO69, PYO103, PlK, SLPl, SL2, S2, UNL-I, wy, Yai, Ya4, Yan, φBE, φCTX, φC17, φKZ, (syn=ΦKZ), φ-LT, Φmu78, φNZ, φPLS-1, φST-1, φW-14, φ-2, 1/72, 2/79, 3, 3/DO, 4/237, 5/406, 6C, 6/6660, 7, 7v, 7/184, 8/280, 9/95, 10/502, 11/DE, 12/100, 12S, 16, 21, 24, 25F, 27, 31, 44, 68, 71, 95, 109, 188, 337, 352, 1214, HN-Pseudomonas (23), A856, B26, CI-I, CI-2, C5, D, gh-1, Fl 16, HF, H90, K5, K6, Kl 04, K109, K166, K267, N4, N5, O6N-25P, PE69, Pf, PPN25, PPN35, PPN89, PPN91, PP2, PP3, PP4, PP6, PP7, PP8, PP56, PP87, PPl 14, PP206, PP207, PP306, PP651, Psp231a, Pssy401, Pssy9220, psi, PTB2, PTB20, PTB42, PXl, PX3, PXlO, PX12, PX14, PYO70, PYO71, R, SH6, SH133, tf, YaS, Ya7, φBS, ΦKf77, φ-MC, ΦmnF82, φPLS27, φPLS743, φS-1, 1, 2, 2, 3, 4, 5, 6, 7, 7, 8, 9, 10, 11, 12, 12B, 13, 14, 15, 14, 15, 16, 17, 18, 19, 20, 20, 21, 21, 22, 23, 23, 24, 25, 31, 53, 73, 119x, 145, 147, 170, 267, 284, 308, 525, NN-Pseudomonas (5), af, A7, B3, B33, B39, BI-I, C22, D3, D37, D40, D62, D3112, F7, FlO, g, gd, ge, gξ Hwl2, Jb 19, KFl, L°, OXN-32P, O6N-52P, PCH-I, PC13-1, PC35-1, PH2, PH51, PH93, PH132, PMW, PM13, PM57, PM61, PM62, PM63, PM69, PM105, PMl 13, PM681, PM682, PO4, PPl, PP4, PPS, PP64, PP65, PP66, PP71, PP86, PP88, PP92, PP401, PP711, PP891, Pssy41, Pssy42, Pssy403, Pssy404, Pssy420, Pssy923, PS4, PS-IO, Pz, SDl, SLl, SL3, SL5, SM, φC5, φCl l, φCl l-1, φC13, φC15, φMO, φX, φO4, φl l, φ240, 2, 2F, 5, 7m, 11, 13, 13/441, 14, 20, 24, 40, 45, 49, 61, 73, 148, 160, 198, 218, 222, 236, 242, 246, 249, 258, 269, 295, 297, 309, 318, 342, 350, 351, 357-1, 400-1, HN-Pseudomonas (6), GlOl, M6, M6a, Ll, PB2, Pssyl5, Pssy4210, Pssy4220, PYO12, PYO34, PYO49, PYO50, PYO51, PYO52, PYO53, PYO57, PYO59, PYO200, PX2, PX5, SL4, φO3, φO6 and 1214.
Bacteria of the genus Rickettsia are infected by the following phage: NN-Rickettsia.
Bacteria of the genus Salmonella are infected by the following phage: b, Beccles, CT, d, Dundee, f, FeIs 2, GI, GUI, GVI, GVIII, k, K, i, j, L, 01, (syn=0-1), (syn=O1), (syn=O-I), (syn=7), 02, 03, P3, P9a, PlO, Sab3, Sab5, SanlS, Sanl7, SI, Taunton, ViI, (syn=ViI), 9, imSalmonella (1), N-I, N-5, N-IO, N-17, N-22, 11, 12, 16-19, 20.2, 36, 449C/C178, 966A/C259, a, B.A.O.R., e, G4, GUI, L, LP7, M, MG40, N-18, PSA68, P4, P9c, P22, (syn=P22), (syn=PLT22), (syn=PLT22), P22al, P22-4, P22-7, P22-11, SNT-I, SNT-2, SP6, Villi, ViIV, ViV, ViVI, ViVII, Worksop, Sj5, ε34, 1, 37, 1(40), (syn=φl[40]), 1, 422, 2, 2.5, 3b, 4, 5, 6, 14(18), 8, 14(6,7), 10, 27, 28B, 30, 31, 32, 33, 34, 36, 37, 39, 1412, SNT-3, 7-11, 40.3, c, C236, C557, C625, C966N, g, GV, G5, Gl 73, h, IRA, Jersey, MB78, P22-1, P22-3, P22-12, Sabl, Sab2, Sab2, Sab4, Sanl, San2, San3, San4, San6, San7, San8, San9, Sanl3, Sanl4, Sanl6, Sanl8, Sanl9, San20, San21, San22, San23, San24, San25, San26, SasLl, SasL2, SasL3, SasL4, SasL5, SlBL, SII, ViII, φl, 1, 2, 3a, 3al, 1010, Ym-Salmonella (1), N-4, SasL6 and 27.
Bacteria of the genus Serratia are infected by the following phage: A2P, PS20, SMB3, SMP, SMP5, SM2, V40, V56, ic, ΦCP-3, ΦCP-6, 3M, 10/la, 20A, 34CC, 34H, 38T, 345G, 345P, 501B, SMB2, SMP2, BC, BT, CW2, CW3, CW4, CW5, Lt232, L2232, L34, L.228, SLP, SMPA, V.43, σ, φCWl, ΦCP6-1, ΦCP6-2, ΦCP6-5, 3T, 5, 8, 9F, 10/1, 2OE, 32/6, 34B, 34CT, 34P, 37, 41, 56, 56D, 56P, 6OP, 61/6, 74/6, 76/4, 101/8900, 226, 227, 228, 229F, 286, 289, 290F, 512, 764a, 2847/10, 2847/1Oa, L.359 and SMBl.
Bacteria of the genus Shigella are infected by the following phage: Fsa, (syn=a), FSD2d, (syn=D2d), (syn=W2d), FSD2E, (syn=W2e), fv, F6, f7.8, H-Sh, PE5, P90, SflI, Sh, SHm, SHrv, (syn=HIV), SHvi, (syn=HVI), SHVvm, (syn=HVIII), SKγ66, (syn=gamma 66), (syn=yββ), (syn=γ66b), SKm, (syn=SIIIb)5 (syn=UI), SKw, (syn=Siva), (syn=IV), SIC™, (syn=SIVA.), (syn=IVA), SKvi, (syn=KVI), (syn=Svi), (syn=VI), SKvm, (syn=Svm), (syn=VIII), SKVIIIA (syn=SvmA), (syn=VIIIA), STvi, STK, STx1, STxn, S66, W2, (syn=D2c), (syn=D20), φl, φIVb 3-SO-R, 8368-SO-R, F7, (syn=FS7), (syn=K29), FlO, (syn=FSlO), (syn=K31), I1, (syn=alfa), (syn=FSa), (syn=Kl 8), (syn=α), I2, (syn=a), (syn=K19), SG33, (syn=G35), (syn=SO-35/G), SG35, (syn=SO-55/G), SG3201, (syn=SO-3201/G), SHn, (syn=HII), SHv, (syn=SHV), SHx, SHX, SKn, (syn=K2), (syn=KII), (syn=Sn), (syn=SsII), (syn=II), SKrv, (syn=Sm), (syn=SsIV), (syn=IV), SK1Va, (syn=Swab), (syn=SsIVa), (syn=IVa), SKV, (syn=K4), (syn=KV), (syn=SV), (syn=SsV), (syn=V), SKx, (syn=K9), (syn=KX), (syn=SX), (syn=SsX), (syn=X), STV, (syn=T35), (syn=35-50-R), STvm, (syn=T8345), (syn=8345-SO-S-R), W1, (syn=D8), (syn=FSD8), W2a, (syn=D2A), (syn=FS2a), DD-2, Sf6, FSi, (syn=Fl), SF6, (syn=F6), SG42, (syn=SO-42/G), SG3203, (syn=SO-3203/G), SKF12, (syn=SsF12), (syn=F12), (syn=F12), STn, (syn=1881-SO-R), γ66, (syn=gamma 66a), (syn=Ssγ66), φ2, BIl, DDVII, (syn=DD7), FSD2b, (syn=W2B), FS2, (syn=F2), (syn=F2), FS4, (syn=F4), (syn=F4), FS5, (syn=F5), (syn=F5), FS9, (syn=F9), (syn=F9), FI l, P2-S0-S, SG36, (syn=SO-36/G), (syn=G36), SG3204, (syn=SO-3204/G), SG3244, (syn=SO-3244/G), SHi, (syn=HI), SHvπ, (syn=HVII), SHK, (syn=HIX), SHx1, SHxπ, (syn=HXn), SKI, KI, (syn=S1), (syn=SsI), SKVII, (syn=KVII), (syn=Svπ), (syn=SsVII), SKIX, (syn=KIX), (syn=S1x), (syn=SsIX), SKXII, (syn=KXII), (syn=Sxn), (syn=SsXII), STi, STffl, STrv, STVi, STvπ, S70, S206, U2-S0-S, 3210-SO-S, 3859-SO-S, 4020-SO-S, φ3, φ5, φ7, φ8, φ9, φlO, φl l, φl3, φl4, φl8, SHm, (syn=Hπi), SHχi, (syn=HXt) and SKxI, (syn=KXI), (syn=Sχi), (syn=SsXI), (syn=XI).
Bacteria of the genus Staphylococcus are infected by the following phage: A, EW, K, Ph5, Ph9, PhIO, Phl3, Pl, P2, P3, P4, P8, P9, PlO, RG, SB-i, (syn=Sb-I), S3K, Twort, ΦSK311, φ812, 06, 40, 58, 119, 130, 131, 200, 1623, STCl, (syn=stcl), STC2, (syn=stc2), 44AHJD, 68, ACl, AC2, A6″C″, A9″C″, b581, CA-I, CA-2, CA-3, CA-4, CA-5, DI l, L39x35, L54a, M42, Nl, N2, N3, N4, N5, N7, N8, NlO, Ni l, N12, N13, N14, N16, Ph6, Phl2, Phl4, UC-18, U4, U15, Sl, S2, S3, S4, S5, X2, Z1, φB5-2, φD, ω, 11, (syn=φl l), (syn=P11-M15), 15, 28, 28A, 29, 31, 31B, 37, 42D, (syn=P42D), 44A, 48, 51, 52, 52A, (syn=P52A), 52B, 53, 55, 69, 71, (syn=P71), 71A, 72, 75, 76, 77, 79, 80, 80α, 82, 82A, 83 A, 84, 85, 86, 88, 88A, 89, 90, 92, 95, 96, 102, 107, 108, 111, 129-26, 130, 130A, 155, 157, 157A, 165, 187, 275, 275A, 275B, 356, 456, 459, 471, 471A, 489, 581, 676, 898, 1139, 1154A, 1259, 1314, 1380, 1405, 1563, 2148, 2638A, 2638B, 2638C, 2731, 2792A, 2792B, 2818, 2835, 2848A, 3619, 5841, 12100, AC3, A8, AlO, A13, b594n, D, HK2, N9, N15, P52, P87, Sl, S6, Z4, φRE, 3A, 3B, 3C, 6, 7, 16, 21, 42B, 42C, 42E, 44, 47, 47A5 47C, 51, 54, 54x1, 70, 73, 75, 78, 81, 82, 88, 93, 94, 101, 105, 110, 115, 129/16, 174, 594n, 1363/14, 2460 and mSStaphylococcus (1).
Bacteria of the genus Streptococcus are infected by the following phage: EJ-I, NN-Streptococais (1), a, Cl, FL0Ths, H39, Cp-I, Cρ-5, Cp-7, Cp-9, Cp-IO, AT298, A5, alO/Jl, alO/J2, alO/J5, alO/J9, A25, BTI l, b6, CAl, c20-l, c20-2, DP-I, Dp-4, DT1, ET42, elO, FA101, FEThs, Fκ, FKKIOI, FKLIO, FKP74, FKH, FLOThs, FyIOl, fl, F10, F20140/76, g, GT-234, HB3, (syn=HB-3), HB-623, HB-746, M102, O1205, φO1205, PST, PO, Pl, P2, P3, P5, P6, P8, P9, P9, P12, P13, P14, P49, P50, P51, P52, P53, P54, P55, P56, P57, P58, P59, P64, P67, P69, P71, P73, P75, P76, P77, P82, P83, P88, sc, sch, sf, SfIl 1, (syn=SFiI 1), (syn=φSFill), (syn=ΦSfil l), (syn=φSfil l), sfil9, (syn=SFil9), (syn=φSFil9), (syn=φSfil9), Sfi21, (syn=SFi21), (syn=φSFi21), (syn=φSfi21), ST0, STX, st2, ST2, ST4, S3, (syn=φS3), s265, Φ17, φ42, Φ57, 80, φ81, φ82, φ83, φ84, φ85, φ86, φ87, φ88, φ89, φ90, φ91, φ92, φ93, φ94, φ95, φ96, φ97, φ98, φ99, φlOO, φlOl, φlO2, φ227, Φ7201, ω1, ω2, ω3, ω4, ω5, ω6, ω8, ωlO, 1, 6, 9, 1OF, 12/12, 14, 17SR, 19S, 24, 50/33, 50/34, 55/14, 55/15, 70/35, 70/36, 71/ST15, 71/45, 71/46, 74F, 79/37, 79/38, 80/J4, 80/J9, 80/ST16, 80/15, 80/47, 80/48, 101, 103/39, 103/40, 121/41, 121/42, 123/43, 123/44, 124/44, 337/ST17 and mStreptococcus (34).
Bacteria of the genus Treponema are infected by the following phage: NN-Treponema (1).
Bacteria of the genus Vibrio are infected by the following phage: CTXφ, fs, (syn=si), fs2, Ivpf5, Vfl2, Vf33, VPIΦ, VSK, v6, 493, CP-Tl, ET25, kappa, K139, Labol,)XN-69P, OXN-86, O6N-21P, PB-I, P147, rp-1, SE3, VA-I, (syn=VcA-I), VcA-2, VP1, VP2, VP4, VP7, VP8, VP9, VPlO, VP17, VP18, VP19, X29, (syn=29 d'Herelle), t, ΦHAWI-1, ΦHAWI-2, ΦHAWI-3, ΦHAWI-4, ΦHAWI-5, ΦHAWI-6, ΦHAWI-7, XHAWI-8, ΦHAWI-9, ΦHAWI-10, ΦHCl-1, ΦHC1-2, ΦHC1-3, ΦHC1-4, ΦHC2-1, >HC2-2, ΦHC2-3, ΦHC2-4, ΦHC3-1, ΦHC3-2, ΦHC3-3, ΦHD1S-1, ΦHD1S-2, ΦHD2S-1, ΦHD2S-2, ΦHD2S-3, ΦHD2S-4, ΦHD2S-5, ΦHDO-1, ΦHDO-2, ΦHDO-3, ΦHDO-4, ΦHDO-5, ΦHDO-6, ΦKL-33, ΦKL-34, ΦKL-35, ΦKL-36, ΦKWH-2, ΦKWH-3, ΦKWH-4, ΦMARQ-1, ΦMARQ-2, ΦMARQ-3, ΦMOAT-1, ΦO139, ΦPEL1A-1, ΦPEL1A-2, ΦPEL8A-1, ΦPEL8A-2, ΦPEL8A-3, ΦPEL8C-1, ΦPEL8C-2, ΦPEL13A-1, ΦPEL13B-1, ΦPEL13B-2, ΦPEL13B-3, ΦPEL13B-4, ΦPEL13B-5, ΦPEL13B-6, ΦPEL13B-7, ΦPEL13B-8, ΦPEL13B-9, ΦPEL13B-10, φVP143, φVP253, Φ16, φl38, 1-II, 5, 13, 14, 16, 24, 32, 493, 6214, 7050, 7227, II, (syn=group II), (syn==φ2), V, VIII, ˜m-Vibrio (13), KVP20, KVP40, nt-1, O6N-22P, P68, el, e2, e3, e4, e5, FK, G, I, K, nt-6, Nl, N2, N3, N4, N5, O6N-34P, OXN-72P, OXN-85P, OXN-100P, P, Ph-I, PL163/10, Q, S, T, φ92, 1-9, 37, 51, 57, 70A-8, 72A-4, 72A-10, 110A-4, 333, 4996, I (syn=group I), III (syn=group III), VI, (syn=A-Saratov), VII, IX, X, HN-Vibrio (6), pAl, 7, 7-8, 70A-2, 71A-6, 72A-5, 72A-8, 108A-10, 109A-6, 109A-8, llOA-1, 110A-5, 110A-7, hv-1, OXN-52P, P13, P38, P53, P65, P108, Pill, TPl3 VP3, VP6, VP12, VP13, 70A-3, 70A-4, 70A-10, 72A-1, 108A-3, 109-B1, 110A-2, 149, (syn=φl49), IV, (syn=group IV), NN-Vibrio (22), VPS, VPIl, VP15, VP16, αl, α2, α3a, α3b, 353B and HN-Vibrio (7).
Bacteria of the genus Yersinia are infected by the following phage: H, H-I, H-2, H-3, H-4, Lucas 110, Lucas 303, Lucas 404, YerA3, YerA7, YerA20, YerA41, 3/M64-76, 5/G394-76, 6/C753-76, 8/C239-76, 9/F18167, 1701, 1710, PST, 1/F2852-76, D+Herelle, EV, H, Kotljarova, PTB, R, Y, YerA41, φYerO3-12, 3, 4/C1324-76, 7/F783-76, 903, 1/M6176 and Yer2AT.
More preferably, the bacteriophage is selected in the group consisting of Salmonella virus SKML39, Shigella virus AG3, Dickeya virus Limestone, Dickeya virus RC2014, Escherichia virus CBA120, Escherichia virus Phaxl, Salmonella virus 38, Salmonella virus Det7, Salmonella virus GG32, Salmonella virus PM10, Salmonella virus SFP10, Salmonella virus SH19, Salmonella virus SJ3, Escherichia virus ECML4, Salmonella virus Marshall, Salmonella virus Maynard, Salmonella virus SJ2, Salmonella virus STML131, Salmonella virus ViI, Erwinia virus Ea2809, Klebsiella virus 0507KN21, Serratia virus IME250, Serratia virus MAM1, Campylobacter virus CP21, Campylobacter virus CP220, Campylobacter virus CPt10, Campylobacter virus IBB35, Campylobacter virus CP81, Campylobacter virus CP30A, Campylobacter virus CPX, Campylobacter virus NCTC12673, Erwinia virus Ea214, Erwinia virus M7, Escherichia virus AYO145A, Escherichia virus EC6, Escherichia virus HY02, Escherichia virus JH2, Escherichia virus TP1, Escherichia virus VpaE1, Escherichia virus wV8, Salmonella virus FelixO1, Salmonella virus HB2014, Salmonella virus Mushroom, Salmonella virus UAB87, Citrobacter virus Moogle, Citrobacter virus Mordin, Escherichia virus SUSP1, Escherichia virus SUSP2, Aeromonas virus phiO18P, Haemophilus virus HP1, Haemophilus virus HP2, Pasteurella virus F108, Vibrio virus K139, Vibrio virus Kappa, Burkholderia virus phi52237, Burkholderia virus phiE122, Burkholderia virus phiE202, Escherichia virus 186, Escherichia virus P4, Escherichia virus P2, Escherichia virus Wphi, Mannheimia virus PHL101, Pseudomonas virus phiCTX, Ralstonia virus RSA1, Salmonella virus Fels2, Salmonella virus PsP3, Salmonella virus SopEphi, Yersinia virus L413C, Staphylococcus virus G1, Staphylococcus virus G15, Staphylococcus virus JD7, Staphylococcus virus K, Staphylococcus virus MCE2014, Staphylococcus virus P108, Staphylococcus virus Rodi, Staphylococcus virus S253, Staphylococcus virus S25-4, Staphylococcus virus SA12, Listeria virus A511, Listeria virus P100, Staphylococcus virus Remus, Staphylococcus virus SA11, Staphylococcus virus Stau2, Bacillus virus Camphawk, Bacillus virus SPO1, Bacillus virus BCP78, Bacillus virus TsarBomba, Staphylococcus virus Twort, Enterococcus virus phiEC24C, Lactobacillus virus Lb338-1, Lactobacillus virus LP65, Enterobacter virus PG7, Escherichia virus CC31, Klebsiella virus JD18, Klebsiella virus PKO111, Escherichia virus Bp7, Escherichia virus IME08, Escherichia virus JS10, Escherichia virus J598, Escherichia virus QL01, Escherichia virus VR5, Enterobacter virus Eap3, Klebsiella virus KP15, Klebsiella virus KP27, Klebsiella virus Matisse, Klebsiella virus Miro, Citrobacter virus Merlin, Citrobacter virus Moon, Escherichia virus JSE, Escherichia virus phil, Escherichia virus RB49, Escherichia virus HX01, Escherichia virus JS09, Escherichia virus RB69, Shigella virus UTAM, Salmonella virus S16, Salmonella virus STML198, Vibrio virus KVP40, Vibrio virus nt1, Vibrio virus ValKK3, Escherichia virus VR7, Escherichia virus VR20, Escherichia virus VR25, Escherichia virus VR26, Shigella virus SP18, Escherichia virus AR1, Escherichia virus C40, Escherichia virus E112, Escherichia virus ECML134, Escherichia virus HY01, Escherichia virus Ime09, Escherichia virus RB3, Escherichia virus RB14, Escherichia virus T4, Shigella virus Pss1, Shigella virus Shfl2, Yersinia virus D1, Yersinia virus PST, Acinetobacter virus 133, Aeromonas virus 65, Aeromonas virus Aeh1, Escherichia virus RB16, Escherichia virus RB32, Escherichia virus RB43, Pseudomonas virus 42, Cronobacter virus CR3, Cronobacter virus CR8, Cronobacter virus CR9, Cronobacter virus PBES02, Pectobacterium virus phiTE, Cronobacter virus GAP31, Escherichia virus 4MG, Salmonella virus SE1, Salmonella virus SSE121, Escherichia virus FFH2, Escherichia virus FV3, Escherichia virus JES2013, Escherichia virus V5, Brevibacillus virus Abouo, Brevibacillus virus Davies, Bacillus virus Agate, Bacillus virus Bobb, Bacillus virus Bp8pC, Erwinia virus Deimos, Erwinia virus Ea35-70, Erwinia virus RAY, Erwinia virus Simmy50, Erwinia virus SpecialG, Acinetobacter virus AB1, Acinetobacter virus AB2, Acinetobacter virus AbC62, Acinetobacter virus AP22, Arthrobacter virus ArV1, Arthrobacter virus Trina, Bacillus virus AvesoBmore, Bacillus virus B4, Bacillus virus Bigbertha, Bacillus virus Riley, Bacillus virus Spock, Bacillus virus Troll, Bacillus virus Bastille, Bacillus virus CAM003, Bacillus virus Bc431, Bacillus virus Bcp1, Bacillus virus BCP82, Bacillus virus BM15, Bacillus virus Deepblue, Bacillus virus JBP901, Burkholderia virus Bcep1, Burkholderia virus Bcep43, Burkholderia virus Bcep781, Burkholderia virus BcepNY3, Xanthomonas virus OP2, Burkholderia virus BcepMu, Burkholderia virus phiE255, Aeromonas virus 44RR2, Mycobacterium virus Alice, Mycobacterium virus Bxz1, Mycobacterium virus Dandelion, Mycobacterium virus HyRo, Mycobacterium virus I3, Mycobacterium virus Nappy, Mycobacterium virus Sebata, Clostridium virus phiC2, Clostridium virus phiCD27, Clostridium virus phiCD119, Bacillus virus CP51, Bacillus virus JL, Bacillus virus Shanette, Escherichia virus CVM10, Escherichia virus ep3, Erwinia virus Asesino, Erwinia virus EaH2, Pseudomonas virus EL, Halomonas virus HAP1, Vibrio virus VP882, Brevibacillus virus Jimmer, Brevibacillus virus Osiris, Pseudomonas virus Ab03, Pseudomonas virus KPP10, Pseudomonas virus PAKP3, Sinorhizobium virus M7, Sinorhizobium virus M12, Sinorhizobium virus N3, Erwinia virus Machina, Arthrobacter virus Brent, Arthrobacter virus Jawnski, Arthrobacter virus Martha, Arthrobacter virus Sonny, Edwardsiella virus MSW3, Edwardsiella virus PEi21, Escherichia virus Mu, Shigella virus SfMu, Halobacterium virus phiH, Bacillus virus Grass, Bacillus virus NIT1, Bacillus virus SPG24, Aeromonas virus 43, Escherichia virus P1, Pseudomonas virus CAb1, Pseudomonas virus CAb02, Pseudomonas virus JG004, Pseudomonas virus PAKP1, Pseudomonas virus PAKP4, Pseudomonas virus PaP1, Burkholderia virus BcepF1, Pseudomonas virus 141, Pseudomonas virus Ab28, Pseudomonas virus DL60, Pseudomonas virus DL68, Pseudomonas virus F8, Pseudomonas virus JG024, Pseudomonas virus KPP12, Pseudomonas virus LBL3, Pseudomonas virus LMA2, Pseudomonas virus PB1, Pseudomonas virus SN, Pseudomonas virus PA7, Pseudomonas virus phiKZ, Rhizobium virus RHEph4, Ralstonia virus RSF1, Ralstonia virus RSL2, Ralstonia virus RSL1, Aeromonas virus 25, Aeromonas virus 31, Aeromonas virus Aes12, Aeromonas virus Aes508, Aeromonas virus AS4, Stenotrophomonas virus IME13, Staphylococcus virus IPLAC1C, Staphylococcus virus SEP1, Salmonella virus SPN3US, Bacillus virus 1, Geobacillus virus GBSV1, Yersinia virus R1RT, Yersinia virus TG1, Bacillus virus G, Bacillus virus PBS1, Microcystis virus Ma-LMM01, Vibrio virus MAR, Vibrio virus VHML, Vibrio virus VP585, Bacillus virus BPS13, Bacillus virus Hakuna, Bacillus virus Megatron, Bacillus virus WPh, Acinetobacter virus AB3, Acinetobacter virus Abp1, Acinetobacter virus Fri1, Acinetobacter virus IME200, Acinetobacter virus PD6A3, Acinetobacter virus PDAB9, Acinetobacter virus phiAB1, Escherichia virus K30, Klebsiella virus K5, Klebsiella virus K11, Klebsiella virus Kp1, Klebsiella virus KP32, Klebsiella virus KpV289, Klebsiella virus F19, Klebsiella virus K244, Klebsiella virus Kp2, Klebsiella virus KP34, Klebsiella virus KpV41, Klebsiella virus KpV71, Klebsiella virus KpV475, Klebsiella virus SU503, Klebsiella virus SU552A, Pantoea virus Limelight, Pantoea virus Limezero, Pseudomonas virus LKA1, Pseudomonas virus phiKMV, Xanthomonas virus f20, Xanthomonas virus f30, Xylella virus Prado, Erwinia virus Era103, Escherichia virus K5, Escherichia virus K1-5, Escherichia virus K1E, Salmonella virus SP6, Escherichia virus T7, Kluyvera virus Kvp1, Pseudomonas virus gh1, Prochlorococcus virus PSSP7, Synechococcus virus P60, Synechococcus virus Syn5, Streptococcus virus Cp1, Streptococcus virus Cp7, Staphylococcus virus 44AHJD, Streptococcus virus C1, Bacillus virus B103, Bacillus virus GA1, Bacillus virus phi29, Kurthia virus 6, Actinomyces virus Av1, Mycoplasma virus P1, Escherichia virus 24B, Escherichia virus 933W, Escherichia virus Min27, Escherichia virus PA28, Escherichia virus Stx2 II, Shigella virus 7502Stx, Shigella virus POCJ13, Escherichia virus 191, Escherichia virus PA2, Escherichia virus TL2011, Shigella virus VASD, Burkholderia virus Bcep22, Burkholderia virus Bcepil02, Burkholderia virus Bcepmigl, Burkholderia virus DC1, Bordetella virus BPP1, Burkholderia virus BcepC6B, Cellulophaga virus Cba41, Cellulophaga virus Cba172, Dinoroseobacter virus DFL12, Erwinia virus Ea9-2, Erwinia virus Frozen, Escherichia virus phiV10, Salmonella virus Epsilon15, Salmonella virus SPN1S, Pseudomonas virus F116, Pseudomonas virus H66, Escherichia virus APECS, Escherichia virus APEC7, Escherichia virus Bp4, Escherichia virus EC1UPM, Escherichia virus ECBP1, Escherichia virus G7C, Escherichia virus IME11, Shigella virusSb1, Achromobacter virus Axp3, Achromobacter virus JWAlpha, Edwardsiella virus KF1, Pseudomonas virus KPP25, Pseudomonas virus R18, Pseudomonas virus Ab09, Pseudomonas virus LIT1, Pseudomonas virus PA26, Pseudomonas virus Ab22, Pseudomonas virus CHU, Pseudomonas virus LUZ24, Pseudomonas virus PAA2, Pseudomonas virus PaP3, Pseudomonas virus PaP4, Pseudomonas virus TL, Pseudomonas virus KPP21, Pseudomonas virus LUZ7, Escherichia virus N4, Salmonella virus 9NA, Salmonella virus SP069, Salmonella virus BTP1, Salmonella virus HK620, Salmonella virus P22, Salmonella virus ST64T, Shigella virus Sf6, Bacillus virus Page, Bacillus virus Palmer, Bacillus virus Pascal, Bacillus virus Pony, Bacillus virus Pookie, Escherichia virus 172-1, Escherichia virus ECB2, Escherichia virus NJ01, Escherichia virus phiEco32, Escherichia virus Septima11, Escherichia virus SU10, Brucella virus Pr, Brucella virus Tb, Escherichia virus Pollock, Salmonella virus FSL SP-058, Salmonella virus FSL SP-076, Helicobacter virus 1961P, Helicobacter virus KHP30, Helicobacter virus KHP40, Hamiltonella virus APSE1, Lactococcus virus KSY1, Phormidium virus WMP3, Phormidium virus WMP4, Pseudomonas virus 119X, Roseobacter virus SIO1, Vibrio virus VpV262, Vibrio virus VC8, Vibrio virus VP2, Vibrio virus VPS, Streptomyces virus Amela, Streptomyces virus phiCAM, Streptomyces virus Aaronocolus, Streptomyces virus Caliburn, Streptomyces virus Danzina, Streptomyces virus Hydra, Streptomyces virus Izzy, Streptomyces virus Lannister, Streptomyces virus Lika, Streptomyces virus Sujidade, Streptomyces virus Zemlya, Streptomyces virus ELB20, Streptomyces virus R4, Streptomyces virus phiHau3, Mycobacterium virus Acadian, Mycobacterium virus Baee, Mycobacterium virus Reprobate, Mycobacterium virus Adawi, Mycobacterium virus Bane1, Mycobacterium virus BrownCNA, Mycobacterium virus Chrisnmich, Mycobacterium virus Cooper, Mycobacterium virus JAMaL, Mycobacterium virus Nigel, Mycobacterium virus Stinger, Mycobacterium virus Vincenzo, Mycobacterium virus Zemanar, Mycobacterium virus Apizium, Mycobacterium virus Manad, Mycobacterium virus Oline, Mycobacterium virus Osmaximus, Mycobacterium virus Pg1, Mycobacterium virus Soto, Mycobacterium virus Suffolk, Mycobacterium virus Athena, Mycobacterium virus Bernardo, Mycobacterium virus Gadjet, Mycobacterium virus Pipefish, Mycobacterium virus Godines, Mycobacterium virus Rosebush, Mycobacterium virus Babsiella, Mycobacterium virus Brujita, Mycobacterium virus Che9c, Mycobacterium virus Sbash, Mycobacterium virus Hawkeye, Mycobacterium virus Plot, Salmonella virus AG11, Salmonella virus Ent1, Salmonella virus f18SE, Salmonella virus Jersey, Salmonella virus L13, Salmonella virus LSPA1, Salmonella virus SE2, Salmonella virus SETP3, Salmonella virus SETP7, Salmonella virus SETP13, Salmonella virus SP101, Salmonella virus SS3e, Salmonella virus wksl3, Escherichia virus K1G, Escherichia virus K1H, Escherichia virus K1ind1, Escherichia virus K1ind2, Salmonella virus SP31, Leuconostoc virus Lmd1, Leuconostoc virus LN03, Leuconostoc virus LN04, Leuconostoc virus LN12, Leuconostoc virus LN6B, Leuconostoc virus P793, Leuconostoc virus 1A4, Leuconostoc virus Ln8, Leuconostoc virus Ln9, Leuconostoc virus LN25, Leuconostoc virus LN34, Leuconostoc virus LNTR3, Mycobacterium virus Bongo, Mycobacterium virus Rey, Mycobacterium virus Butters, Mycobacterium virus Michelle, Mycobacterium virus Charlie, Mycobacterium virus Pipsqueaks, Mycobacterium virus Xeno, Mycobacterium virus Panchino, Mycobacterium virus Phrann, Mycobacterium virus Redi, Mycobacterium virus Skinnyp, Gordonia virus BaxterFox, Gordonia virus Yeezy, Gordonia virus Kita, Gordonia virus Zirinka, Gorrdonia virus Nymphadora, Mycobacterium virus Bignuz, Mycobacterium virus Brusacoram, Mycobacterium virus Donovan, Mycobacterium virus Fishburne, Mycobacterium virus Jebeks, Mycobacterium virus Malithi, Mycobacterium virus Phayonce, Enterobacter virus F20, Klebsiella virus 1513, Klebsiella virus KLPN1, Klebsiella virus KP36, Klebsiella virus PKP126, Klebsiella virus Sushi, Escherichia virus AHP42, Escherichia virus AHS24, Escherichia virus AKS96, Escherichia virus C119, Escherichia virus E41c, Escherichia virus Eb49, Escherichia virus Jk06, Escherichia virus KP26, Escherichia virus Rogue1, Escherichia virus ACGM12, Escherichia virus Rtp, Escherichia virus ADB2, Escherichia virus JMPW1, Escherichia virus JMPW2, Escherichia virus T1, Shigella virus PSf2, Shigella virus Shfl 1, Citrobacter virus Stevie, Escherichia virus TLS, Salmonella virus SP126, Cronobacter virus Esp2949-1, Pseudomonas virus Ab18, Pseudomonas virus Ab19, Pseudomonas virus PaMx11, Arthrobacter virus Amigo, Propionibacterium virus Anatole, Propionibacterium virus B3, Bacillus virus Andromeda, Bacillus virus Blastoid, Bacillus virus Curly, Bacillus virus Eoghan, Bacillus virus Finn, Bacillus virus Glittering, Bacillus virus Riggi, Bacillus virus Taylor, Gordonia virus Attis, Mycobacterium virus Barnyard, Mycobacterium virus Konstantine, Mycobacterium virus Predator, Mycobacterium virus Bernal13, Staphylococcus virus 13, Staphylococcus virus 77, Staphylococcus virus 108PVL, Mycobacterium virus Bron, Mycobacterium virus Faith1, Mycobacterium virus Joedirt, Mycobacterium virus Rumpelstiltskin, Lactococcus virus bIL67, Lactococcus virus c2, Lactobacillus virus c5, Lactobacillus virus Ld3, Lactobacillus virus Ld17, Lactobacillus virus Ld25A, Lactobacillus virus LLKu, Lactobacillus virus phiLdb, Cellulophaga virus Cba121, Cellulophaga virus Cba171, Cellulophaga virus Cba181, Cellulophaga virus ST, Bacillus virus 250, Bacillus virus IEBH, Mycobacterium virus Ardmore, Mycobacterium virus Avani, Mycobacterium virus Boomer, Mycobacterium virus Che8, Mycobacterium virus Che9d, Mycobacterium virus Deadp, Mycobacterium virus Dlane, Mycobacterium virus Dorothy, Mycobacterium virus Dotproduct, Mycobacterium virus Drago, Mycobacterium virus Fruitloop, Mycobacterium virus Gumbie, Mycobacterium virus Ibhubesi, Mycobacterium virus Llij, Mycobacterium virus Mozy, Mycobacterium virus Mutaforma13, Mycobacterium virus Pacc40, Mycobacterium virus PMC, Mycobacterium virus Ramsey, Mycobacterium virus Rockyhorror, Mycobacterium virus SG4, Mycobacterium virus Shauna1, Mycobacterium virus Shilan, Mycobacterium virus Spartacus, Mycobacterium virus Taj, Mycobacterium virus Tweety, Mycobacterium virus Wee, Mycobacterium virus Yoshi, Salmonella virus Chi, Salmonella virus FSLSP030, Salmonella virus FSLSP088, Salmonella virus iEPS5, Salmonella virus SPN19, Mycobacterium virus 244, Mycobacterium virus Bask21, Mycobacterium virus CJW1, Mycobacterium virus Eureka, Mycobacterium virus Kostya, Mycobacterium virus Porky, Mycobacterium virus Pumpkin, Mycobacterium virus Sirduracell, Mycobacterium virus Toto, Mycobacterium virus Corndog, Mycobacterium virus Firecracker, Rhodobacter virus RcCronus, Pseudomonas virus D3112, Pseudomonas virus DMS3, Pseudomonas virus FHA0480, Pseudomonas virus LPB1, Pseudomonas virus MP22, Pseudomonas virus MP29, Pseudomonas virus MP38, Pseudomonas virus PA1KOR, Pseudomonas virus D3, Pseudomonas virus PMG1, Arthrobacter virus Decurro, Gordonia virus Demosthenes, Gordonia virus Katyusha, Gordonia virus Kvothe, Propionibacterium virus B22, Propionibacterium virus Doucette, Propionibacterium virus E6, Propionibacterium virus G4, Burkholderia virus phi6442, Burkholderia virus phi1026b, Burkholderia virus phiE125, Edwardsiella virus eiAU, Mycobacterium virus Ff47, Mycobacterium virus Muddy, Mycobacterium virus Gaia, Mycobacterium virus Giles, Arthrobacter virus Captnmurica, Arthrobacter virus Gordon, Gordonia virus GordTnk2, Paenibacillus virus Harrison, Escherichia virus EK99P1, Escherichia virus HK578, Escherichia virus JL1, Escherichia virus SSL2009a, Escherichia virus YD2008s, Shigella virus EP23, Sodalis virus SO1, Escherichia virus HK022, Escherichia virus HK75, Escherichia virus HK97, Escherichia virus HK106, Escherichia virus HK446, Escherichia virus HK542, Escherichia virus HK544, Escherichia virus HK633, Escherichia virus mEp234, Escherichia virus mEp235, Escherichia virus mEpX1, Escherichia virus mEpX2, Escherichia virus mEp043, Escherichia virus mEp213, Escherichia virus mEp237, Escherichia virus mEp390, Escherichia virus mEp460, Escherichia virus mEp505, Escherichia virus mEp506, Brevibacillus virus Jenst, Achromobacter virus 83-24, Achromobacter virus JWX, Arthrobacter virus Kellezzio, Arthrobacter virus Kitkat, Arthrobacter virus Bennie, Arthrobacter virus DrRobert, Arthrobacter virus Glenn, Arthrobacter virus HunterDalle, Arthrobacter virus Joann, Arthrobacter virus Korra, Arthrobacter virus Preamble, Arthrobacter virus Pumancara, Arthrobacter virus Wayne, Mycobacterium virus Alma, Mycobacterium virus Arturo, Mycobacterium virus Astro, Mycobacterium virus Backyardigan, Mycobacterium virus BBPiebs31, Mycobacterium virus Benedict, Mycobacterium virus Bethlehem, Mycobacterium virus Billknuckles, Mycobacterium virus Bruns, Mycobacterium virus Bxb1, Mycobacterium virus Bxz2, Mycobacterium virus Che12, Mycobacterium virus Cuco, Mycobacterium virus D29, Mycobacterium virus Doom, Mycobacterium virus Ericb, Mycobacterium virus Euphoria, Mycobacterium virus George, Mycobacterium virus Gladiator, Mycobacterium virus Goose, Mycobacterium virus Hammer, Mycobacterium virus Heldan, Mycobacterium virus Jasper, Mycobacterium virus JC27, Mycobacterium virus Jeffabunny, Mycobacterium virus JHC117, Mycobacterium virus KBG, Mycobacterium virus Kssjeb, Mycobacterium virus Kugel, Mycobacterium virus L5, Mycobacterium virus Lesedi, Mycobacterium virus LHTSCC, Mycobacterium virus lockley, Mycobacterium virus Marcell, Mycobacterium virus Microwolf, Mycobacterium virus Mrgordo, Mycobacterium virus Museum, Mycobacterium virus Nepal, Mycobacterium virus Packman, Mycobacterium virus Peaches, Mycobacterium virus Perseus, Mycobacterium virus Pukovnik, Mycobacterium virus Rebeuca, Mycobacterium virus Redrock, Mycobacterium virus Ridgecb, Mycobacterium virus Rockstar, Mycobacterium virus Saintus, Mycobacterium virus Skipole, Mycobacterium virus Solon, Mycobacterium virus Switzer, Mycobacterium virus SWU1, Mycobacterium virus Ta17a, Mycobacterium virus Tiger, Mycobacterium virus Timshel, Mycobacterium virus Trixie, Mycobacterium virus Turbido, Mycobacterium virus Twister, Mycobacterium virus U2, Mycobacterium virus Violet, Mycobacterium virus Wonder, Escherichia virus DE3, Escherichia virus HK629, Escherichia virus HK630, Escherichia virus lambda, Arthrobacter virus Laroye, Mycobacterium virus Halo, Mycobacterium virus Liefie, Mycobacterium virus Marvin, Mycobacterium virus Mosmoris, Arthrobacter virus Circum, Arthrobacter virus Mudcat, Escherichia virus N15, Escherichia virus 9g, Escherichia virus JenK1, Escherichia virus JenP1, Escherichia virus JenP2, Pseudomonas virus NP1, Pseudomonas virus PaMx25, Mycobacterium virus Baka, Mycobacterium virus Courthouse, Mycobacterium virus Littlee, Mycobacterium virus Omega, Mycobacterium virus Optimus, Mycobacterium virus Thibault, Polaribacter virus P12002L, Polaribacter virus P12002S, Nonlabens virus P12024L, Nonlabens virus P12024S, Thermus virus P23-45, Thermus virus P74-26, Listeria virus LP26, Listeria virus LP37, Listeria virus LP110, Listeria virus LP114, Listeria virus P70, Propionibacterium virus ATCC29399BC, Propionibacterium virus ATCC29399BT, Propionibacterium virus Attacne, Propionibacterium virus Keiki, Propionibacterium virus Kubed, Propionibacterium virus Lauchelly, Propionibacterium virus MrAK, Propionibacterium virus Ouroboros, Propionibacterium virus P91, Propionibacterium virus P105, Propionibacterium virus P144, Propionibacterium virus P1001, Propionibacterium virus P1.1, Propionibacterium virus P100A, Propionibacterium virus P100D, Propionibacterium virus P101A, Propionibacterium virus P104A, Propionibacterium virus PA6, Propionibacterium virus Pacnes201215, Propionibacterium virus PAD20, Propionibacterium virus PAS50, Propionibacterium virus PHL009M11, Propionibacterium virus PHL025M00, Propionibacterium virus PHL037M02, Propionibacterium virus PHL041M10, Propionibacterium virus PHL060L00, Propionibacterium virus PHL067M01, Propionibacterium virus PHL070N00, Propionibacterium virus PHL071N05, Propionibacterium virus PHL082M03, Propionibacterium virus PHL092M00, Propionibacterium virus PHL095N00, Propionibacterium virus PHL111M01, Propionibacterium virus PHL112N00, Propionibacterium virus PHL113M01, Propionibacterium virus PHL114L00, Propionibacterium virus PHL116M00, Propionibacterium virus PHL117M00, Propionibacterium virus PHL117M01, Propionibacterium virus PHL132N00, Propionibacterium virus PHL141N00, Propionibacterium virus PHL151M00, Propionibacterium virus PHL151N00, Propionibacterium virus PHL152M00, Propionibacterium virus PHL163M00, Propionibacterium virus PHL171M01, Propionibacterium virus PHL179M00, Propionibacterium virus PHL194M00, Propionibacterium virus PHL199M00, Propionibacterium virus PHL301M00, Propionibacterium virus PHL308M00, Propionibacterium virus Pirate, Propionibacterium virus Procrass1, Propionibacterium virus SKKY, Propionibacterium virus Solid, Propionibacterium virus Stormborn, Propionibacterium virus Wizzo, Pseudomonas virus PaMx28, Pseudomonas virus PaMx74, Mycobacterium virus Patience, Mycobacterium virus PBI1, Rhodococcus virus Pepy6, Rhodococcus virus Poco6, Propionibacterium virus PFR1, Streptomyces virus phiBT1, Streptomyces virus phiC31, Streptomyces virus TG1, Caulobacter virus Karma, Caulobacter virus Magneto, Caulobacter virus phiCbK, Caulobacter virus Rogue, Caulobacter virus Swift, Staphylococcus virus 11, Staphylococcus virus 29, Staphylococcus virus 37, Staphylococcus virus 53, Staphylococcus virus 55, Staphylococcus virus 69, Staphylococcus virus 71, Staphylococcus virus 80, Staphylococcus virus 85, Staphylococcus virus 88, Staphylococcus virus 92, Staphylococcus virus 96, Staphylococcus virus 187, Staphylococcus virus 52a, Staphylococcus virus 80alpha, Staphylococcus virus CNPH82, Staphylococcus virus EW, Staphylococcus virus IPLA5, Staphylococcus virus IPLA7, Staphylococcus virus IPLA88, Staphylococcus virus PH15, Staphylococcus virus phiETA, Staphylococcus virus phiETA2, Staphylococcus virus phiETA3, Staphylococcus virus phiMR11, Staphylococcus virus phiMR25, Staphylococcus virus phiNM1, Staphylococcus virus phiNM2, Staphylococcus virus phiNM4, Staphylococcus virus SAP26, Staphylococcus virus X2, Enterococcus virus FL1, Enterococcus virus FL2, Enterococcus virus FL3, Lactobacillus virus ATCC8014, Lactobacillus virus phiJL1, Pediococcus virus cIP1, Aeromonas virus pIS4A, Listeria virus LP302, Listeria virus PSA, Methanobacterium virus psiM1, Roseobacter virus RDJL1, Roseobacter virus RDJL2, Rhodococcus virus RER2, Enterococcus virus BC611, Enterococcus virus IMEEF1, Enterococcus virus SAP6, Enterococcus virus VD13, Streptococcus virus SPQS1, Mycobacterium virus Papyrus, Mycobacterium virus Send513, Burkholderia virus KL1, Pseudomonas virus 73, Pseudomonas virus Ab26, Pseudomonas virus Kakheti25, Escherichia virus Cajan, Escherichia virus Seurat, Staphylococcus virus SEP9, Staphylococcus virus Sextaec, Streptococcus virus 858, Streptococcus virus 2972, Streptococcus virus ALQ132, Streptococcus virus O1205, Streptococcus virus Sfi11, Streptococcus virus 7201, Streptococcus virus DT1, Streptococcus virus phiAbc2, Streptococcus virus Sfi19, Streptococcus virus Sfi21, Paenibacillus virus Diva, Paenibacillus virus Hb10c2, Paenibacillus virus Rani, Paenibacillus virus Shelly, Paenibacillus virus Sitara, Paenibacillus virus Willow, Lactococcus virus 712, Lactococcus virus ASCC191, Lactococcus virus ASCC273, Lactococcus virus ASCC281, Lactococcus virus ASCC465, Lactococcus virus ASCC532, Lactococcus virus Bibb29, Lactococcus virus bIL170, Lactococcus virus CB13, Lactococcus virus CB14, Lactococcus virus CB19, Lactococcus virus CB20, Lactococcus virus jj50, Lactococcus virus P2, Lactococcus virus P008, Lactococcus virus sk1, Lactococcus virus S14, Bacillus virus Slash, Bacillus virus Stahl, Bacillus virus Staley, Bacillus virus Stills, Gordonia virus Bachita, Gordonia virus ClubL, Gordonia virus OneUp, Gordonia virus Smoothie, Gordonia virus Soups, Bacillus virus SPbeta, Vibrio virus MAR10, Vibrio virus SSP002, Escherichia virus AKFV33, Escherichia virus BF23, Escherichia virus DT57C, Escherichia virus EPS7, Escherichia virus FFH1, Escherichia virus H8, Escherichia virus slur09, Escherichia virus T5, Salmonella virus 118970sal2, Salmonella virus Shivani, Salmonella virus SPC35, Salmonella virus Stitch, Arthrobacter virus Tank, Tsukamurella virus TIN2, Tsukamurella virus TIN3, Tsukamurella virus TIN4, Rhodobacter virus RcSpartan, Rhodobacter virus RcTitan, Mycobacterium virus Anaya, Mycobacterium virus Angelica, Mycobacterium virus Crimd, Mycobacterium virus Fionnbarth, Mycobacterium virus Jaws, Mycobacterium virus Larva, Mycobacterium virus Macncheese, Mycobacterium virus Pixie, Mycobacterium virus TM4, Bacillus virus BMBtp2, Bacillus virus TP21, Geobacillus virus Tp84, Staphylococcus virus 47, Staphylococcus virus 3a, Staphylococcus virus 42e, Staphylococcus virus IPLA35, Staphylococcus virus phi12, Staphylococcus virus phiSLT, Mycobacterium virus 32HC, Rhodococcus virus RGL3, Paenibacillus virus Vegas, Gordonia virus Vendetta, Bacillus virus Wbeta, Mycobacterium virus Wildcat, Gordonia virus Twister6, Gordonia virus Wizard, Gordonia virus Hotorobo, Gordonia virus Monty, Gordonia virus Woes, Xanthomonas virus CP1, Xanthomonas virus OP1, Xanthomonas virus phl17, Xanthomonas virus Xop411, Xanthomonas virus Xp10, Streptomyces virus TP1604, Streptomyces virus YDN12, Alphaproteobacteria virus phiJ1001, Pseudomonas virus LKO4, Pseudomonas virus M6, Pseudomonas virus MP1412, Pseudomonas virus PAE1, Pseudomonas virus Yua, Pseudoalteromonas virus PM2, Pseudomonas virus phi6, Pseudomonas virus phi8, Pseudomonas virus phi12, Pseudomonas virus phi13, Pseudomonas virus phi2954, Pseudomonas virus phiNN, Pseudomonas virus phiYY, Vibrio virus fs1, Vibrio virus VGJ, Ralstonia virus RS603, Ralstonia virus RSM1, Ralstonia virus RSM3, Escherichia virus M13, Escherichia virus I22, Salmonella virus IKe, Acholeplasma virus L51, Vibrio virus fs2, Vibrio virus VFJ, Escherichia virus If1, Propionibacterium virus B5, Pseudomonas virus Pf1, Pseudomonas virus Pf3, Ralstonia virus PE226, Ralstonia virus RSS1, Spiroplasma virus SVTS2, Stenotrophomonas virus PSH1, Stenotrophomonas virus SMA6, Stenotrophomonas virus SMA7, Stenotrophomonas virus SMA9, Vibrio virus CTXphi, Vibrio virus KSF1, Vibrio virus VCY, Vibrio virus Vf33, Vibrio virus VfO3K6, Xanthomonas virus Cf1c, Spiroplasma virus C74, Spiroplasma virus R8A2B, Spiroplasma virus SkV1CR23x, Escherichia virus FI, Escherichia virus Qbeta, Escherichia virus BZ13, Escherichia virus MS2, Escherichia virus alpha3, Escherichia virus ID21, Escherichia virus ID32, Escherichia virus ID62, Escherichia virus NC28, Escherichia virus NC29, Escherichia virus NC35, Escherichia virus phiK, Escherichia virus St1, Escherichia virus WA45, Escherichia virus G4, Escherichia virus ID52, Escherichia virus Talmos, Escherichia virus phiX174, Bdellovibrio virus MAC1, Bdellovibrio virus MH2K, Chlamydia virus Chp1, Chlamydia virus Chp2, Chlamydia virus CPAR39, Chlamydia virus CPG1, Spiroplasma virus SpV4, Acholeplasma virus L2, Pseudomonas virus PR4, Pseudomonas virus PRD1, Bacillus virus AP50, Bacillus virus Bam35, Bacillus virus GIL16, Bacillus virus Wip1, Escherichia virus phi80, Escherichia virus RB42, Escherichia virus T2, Escherichia virus T3, Escherichia virus T6, Escherichia virus VT2-Sa, Escherichia virus VT1-Sakai, Escherichia virus VT2-Sakai, Escherichia virus CP-933V, Escherichia virus P27, Escherichia virus Stx2phi-I, Escherichia virus Stx1phi, Escherichia virus Stx2phi-II, Escherichia virus CP-1639, based on the Escherichia virus BP-4795, Escherichia virus 86, Escherichia virus Min27, Escherichia virus 2851, Escherichia virus 1717, Escherichia virus YYZ-2008, Escherichia virus ECO26_P06, Escherichia virus ECO103_P15, Escherichia virus ECO103_P12, Escherichia virus ECO111_P16, Escherichia virus ECO111_P11, Escherichia virus VT2phi_272, Escherichia virus TL-2011c, Escherichia virus P13374, Escherichia virus Sp5.
In one embodiment, the bacterial virus particles target E. coli and includes the capsid of a bacteriophage selected in the group consisting of BW73, B278, D6, D108, E, El, E24, E41, FI-2, FI-4, FI-5, HI8A, Ffl8B, i, MM, Mu, 025, PhI-5, Pk, PSP3, Pl, PlD, P2, P4, Sl, Wφ, φK13, φl, φ2, φ7, φ92, 7 A, 8φ, 9φ, 18, 28-1, 186, 299, HH-Escherichia (2), AB48, CM, C4, C16, DD-VI, E4, E7, E28, FE, FI3, H, Hl, H3, H8, K3, M, N, ND-2, ND-3, ND4, ND-5, ND6, ND-7, Ox-I, Ox-2, Ox-3, Ox-4, Ox-5, Ox-6, PhI-I, RB42, RB43, RB49, RB69, S, SaI-I, Sal-2, Sal-3, Sal-4, Sal-5, Sal-6, TC23, TC45, TuII*-6, TuIP-24, TuII*46, TuIP-60, T2, T4, T6, T35, αl, 1, IA, 3, 3A, 3T+, 5φ, 9266Q, CFO103, HK620, J, K, KlF, m59, no. A, no. E, no. 3, no. 9, N4, sd, T3, T7, WPK, W31, ΔH, φC3888, φK3, φK7, φK12, φV-1, Φ04-CF, Φ05, Φ06, Φ07, φl, φl.2, φ20, φ95, φ263, φlO92, φl, φll, Ω8, 1, 3, 7, 8, 26, 27, 28-2, 29, 30, 31, 32, 38, 39, 42, 933W, NN-Escherichia (1), Esc-7-11, AC30, CVX-5, Cl, DDUP, ECl, EC2, E21, E29, Fl, F26S, F27S, Hi, HK022, HK97, HK139, HK253, HK256, K7, ND-I, PA-2, q, S2, Tl,), T3C, T5, UC-I, w, β4, γ2, γ, ΦD326, φγ, Φ06, Φ7, Φ10, φ80, χ, 2, 4, 4A, 6, 8A, 102, 150, 168, 174, 3000, AC6, AC7, AC28, AC43, AC50, AC57, AC81, AC95, HK243, KlO, ZG/3A, 5, 5A, 21EL, H19-J and 933H.
Prebiotics include, but are not limited to, amino acids, biotin, fructo-oligosaccharide, galacto-oligosaccharides, hemicelluloses (e.g., arabinoxylan, xylan, xyloglucan, and glucomannan), inulin, chitin, lactulose, mannan oligosaccharides, oligofructose-enriched inulin, gums (e.g., guar gum, gum arabic and carregenaan), oligofructose, oligodextrose, tagatose, resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide, pectins (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fibers (e.g., soy fiber, sugarbeet fiber, pea fiber, corn bran, and oat fiber) and xylooligosaccharides.
Probiotics include, but are not limited to lactobacilli, bifidobacteria, streptococci, enterococci, propionibacteria, saccaromycetes, lactobacilli, bifidobacteria, or proteobacteria.
The antibiotic can be selected from the group consisting in penicillins such as penicillin G, penicillin K, penicillin N, penicillin O, penicillin V, methicillin, benzylpenicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, ampicillin, amoxicillin, pivampicillin, hetacillin, bacampicillin, metampicillin, talampicillin, epicillin, carbenicillin, ticarcillin, temocillin, mezlocillin, and piperacillin; cephalosporins such as cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cefalotin, cefapirin, cefatrizine, cefazaflur, cefazedone, cefazolin, cefradine, cefroxadine, ceftezole, cefaclor, cefonicid, cefprozil, cefuroxime, cefuzonam, cefmetazole, cefotetan, cefoxitin, loracarbef, cefbuperazone, cefminox, cefotetan, cefoxitin, cefotiam, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefixime, cefmenoxime, cefodizime, cefotaxime, cefovecin, cefpimizole, cefpodoxime, cefteram, ceftamere, ceftibuten, ceftiofur, ceftiolene, ceftizoxime, ceftriaxone, cefoperazone, ceftazidime, latamoxef, cefclidine, cefepime, cefluprenam, cefoselis, cefozopran, cefpirome, cefquinome, flomoxef, ceftobiprole, ceftaroline, ceftolozane, cefaloram, cefaparole, cefcanel, cefedrolor, cefempidone, cefetrizole, cefivitril, cefmatilen, cefmepidium, cefoxazole, cefrotil, cefsumide, ceftioxide, cefuracetime, and nitrocefin; polymyxins such as polysporin, neosporin, polymyxin B, and polymyxin E, rifampicins such as rifampicin, rifapentine, and rifaximin; Fidaxomicin; quinolones such as cinoxacin, nalidixic acid, oxolinic acid, piromidic acid, pipemidic acid, rosoxacin, ciprofloxacin, enoxacin, fleroxacin, lomefloxacin, nadifloxacin, norfloxacin, ofloxacin, pefloxacin, rufloxacin, balofloxacin, grepafloxacin, levofloxacin, pazufloxacin, temafloxacin, tosufloxacin, clinafloxacin, gatifloxacin, gemifloxacin, moxifloxacin, sitafloxacin, trovafloxacin, prulifloxacin, delafloxacin, nemonoxacin, and zabofloxacin; sulfonamides such as sulfafurazole, sulfacetamide, sulfadiazine, sulfadimidine, sulfafurazole, sulfisomidine, sulfadoxine, sulfamethoxazole, sulfamoxole, sulfanitran, sulfadimethoxine, sulfamethoxypyridazine, sulfametoxydiazine, sulfadoxine, sulfametopyrazine, and terephtyl; macrolides such as azithromycin, clarithromycin, erythromycin, fidaxomicin, telithromycin, carbomycin A, josamycin, kitasamycin, midecamycin, oleandomycin, solithromycin, spiramycin, troleandomycin, tylosin, and roxithromycin; ketolides such as telithromycin, and cethromycin; lluoroketolides such as solithromycin; lincosamides such as lincomycin, clindamycin, and pirlimycin; tetracyclines such as demeclocycline, doxycycline, minocycline, oxytetracycline, and tetracycline; aminoglycosides such as amikacin, dibekacin, gentamicin, kanamycin, neomycin, netilmicin, sisomicin, tobramycin, paromomycin, and streptomycin; ansamycins such as geldanamycin, herbimycin, and rifaximin; carbacephems such as loracarbef; carbapenems such as ertapenem, doripenem, imipenem (or cilastatin), and meropenem; glycopeptides such as teicoplanin, vancomycin, telavancin, dalbavancin, and oritavancin; lincosamides such as clindamycin and lincomycin; lipopeptides such as daptomycin; monobactams such as aztreonam; nitrofurans such as furazolidone, and nitrofurantoin; oxazolidinones such as linezolid, posizolid, radezolid, and torezolid; teixobactin, clofazimine, dapsone, capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, pyrazinamide, rifabutin, arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin (or dalfopristin), thiamphenicol, tigecycline, tinidazole, trimethoprim, alatrofloxacin, fidaxomycin, nalidixice acide, rifampin, derivatives and combination thereof.
The present invention provides pharmaceutical or veterinary compositions comprising one or more of the bacterial delivery vehicles disclosed herein and a pharmaceutically-acceptable carrier. Generally, for pharmaceutical use, the bacterial delivery vehicles may be formulated as a pharmaceutical preparation or compositions comprising at least one bacterial delivery vehicles and at least one pharmaceutically acceptable carrier, diluent or excipient, and optionally one or more further pharmaceutically active compounds. Such a formulation may be in a form suitable for oral administration, for parenteral administration (such as by intravenous, intramuscular or subcutaneous injection or intravenous infusion), for topical administration, for administration by inhalation, by a skin patch, by an implant, by a suppository, etc. Such administration forms may be solid, semi-solid or liquid, depending on the manner and route of administration. For example, formulations for oral administration may be provided with an enteric coating that will allow the synthetic bacterial delivery vehicles in the formulation to resist the gastric environment and pass into the intestines. More generally, synthetic bacterial delivery vehicle formulations for oral administration may be suitably formulated for delivery into any desired part of the gastrointestinal tract. In addition, suitable suppositories may be used for delivery into the gastrointestinal tract. Various pharmaceutically acceptable carriers, diluents and excipients useful in bacterial delivery vehicle compositions are known to the skilled person.
Also provided are methods for treating a bacterial infection using the synthetic bacterial delivery vehicles disclosed herein. The methods include administering the synthetic bacterial delivery vehicles or compositions disclosed herein to a subject having a bacterial infection in need of treatment. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.
The pharmaceutical or veterinary composition according to the disclosure may further comprise a pharmaceutically acceptable vehicle. A solid pharmaceutically acceptable vehicle may include one or more substances which may also act as flavouring agents, lubricants, solubilisers, suspending agents, dyes, fillers, glidants, compression aids, inert binders, sweeteners, preservatives, dyes, coatings, or tablet-disintegrating agents. Suitable solid vehicles include, for example calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.
The pharmaceutical or veterinary composition may be prepared as a sterile solid composition that may be suspended at the time of administration using sterile water, saline, or other appropriate sterile injectable medium. The pharmaceutical or veterinary compositions of the disclosure may be administered orally in the form of a sterile solution or suspension containing other solutes or suspending agents (for example, enough saline or glucose to make the solution isotonic), bile salts, acacia, gelatin, sorbitan monoleate, polysorbate 8o (oleate esters of sorbitol and its anhydrides copolymerized with ethylene oxide) and the like. The particles according to the disclosure can also be administered orally either in liquid or solid composition form. Compositions suitable for oral administration include solid forms, such as pills, capsules, granules, tablets, and powders, and liquid forms, such as solutions, syrups, elixirs, and suspensions. Forms useful for enteral administration include sterile solutions, emulsions, and suspensions.
The bacterial delivery vehicles according to the disclosure may be dissolved or suspended in a pharmaceutically acceptable liquid vehicle such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats. The liquid vehicle can contain other suitable pharmaceutical additives such as solubilisers, emulsifiers, buffers, preservatives, sweeteners, flavouring agents, suspending agents, thickening agents, colours, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid vehicles for oral and enteral administration include water (partially containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil). For parenteral administration, the vehicle can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid vehicles are useful in sterile liquid form compositions for enteral administration. The liquid vehicle for pressurized compositions can be a halogenated hydrocarbon or other pharmaceutically acceptable propellant.
For transdermal administration, the pharmaceutical or veterinary composition can be formulated into ointment, cream or gel form and appropriate penetrants or detergents could be used to facilitate permeation, such as dimethyl sulfoxide, dimethyl acetamide and dimethylformamide.
For transmucosal administration, nasal sprays, rectal or vaginal suppositories can be used. The active compounds can be incorporated into any of the known suppository bases by methods known in the art. Examples of such bases include cocoa butter, polyethylene glycols (carbowaxes), polyethylene sorbitan monostearate, and mixtures of these with other compatible materials to modify the melting point or dissolution rate.
The diseases or disorders caused by bacteria may be selected from the group consisting of abdominal cramps, acne vulgaris, acute epiglottitis, arthritis, bacteraemia, bloody diarrhea, botulism, Brucellosis, brain abscess, chancroid venereal disease, Chlamydia, Crohn's disease, conjunctivitis, cholecystitis, colorectal cancer, polyposis, dysbiosis, Lyme disease, diarrhea, diphtheria, duodenal ulcers, endocarditis, erysipelothricosis, enteric fever, fever, glomerulonephritis, gastroenteritis, gastric ulcers, Guillain-Barre syndrome tetanus, gonorrhoea, gingivitis, inflammatory bowel diseases, irritable bowel syndrome, leptospirosis, leprosy, listeriosis, tuberculosis, Lady Widermere syndrome, Legionaire's disease, meningitis, mucopurulent conjunctivitis, multi-drug resistant bacterial infections, multi-drug resistant bacterial carriage, myonecrosis-gas gangrene, Mycobacterium avium complex, neonatal necrotizing enterocolitis, nocardiosis, nosocomial infection, otitis, periodontitis, phalyngitis, pneumonia, peritonitis, purpuric fever, Rocky Mountain spotted fever, shigellosis, syphilis, sinusitis, sigmoiditis, septicaemia, subcutaneous abscesses, tularaemia, tracheobronchitis, tonsillitis, typhoid fever, ulcerative colitis, urinary infection, whooping cough.
The infection caused by bacteria may be selected from the group consisting of skin infections such as acne, intestinal infections such as esophagitis, gastritis, enteritis, colitis, sigmoiditis, rectitis, and peritonitis, urinary tract infections, vaginal infections, female upper genital tract infections such as salpingitis, endometritis, oophoritis, myometritis, parametritis and infection in the pelvic peritoneum, respiratory tract infections such as pneumonia, intra-amniotic infections, odontogenic infections, endodontic infections, fibrosis, meningitis, bloodstream infections, nosocomial infection such as catheter-related infections, hospital acquired pneumonia, post-partum infection, hospital acquired gastroenteritis, hospital acquired urinary tract infections, or a combination thereof. Preferably, the infection according to the disclosure is caused by a bacterium presenting an antibiotic resistance. In a particular embodiment, the infection is caused by a bacterium as listed above in the targeted bacteria.
The disclosure concerns a pharmaceutical or veterinary composition for use in the treatment of metabolic disorder including, for example, obesity and diabetes.
In a particular embodiment, the disclosure concerns a pharmaceutical or veterinary composition for use in the treatment of pathologies involving bacteria of the human microbiome, such as inflammatory and auto-immune diseases, cancers, infections or brain disorders. Indeed, some bacteria of the microbiome, without triggering any infection, can secrete molecules that will induce and/or enhance inflammatory or auto-immune diseases or cancer development. More specifically, the present disclosure relates also to modulating microbiome composition to improve the efficacy of immunotherapies based, for example, on CAR-T (Chimeric Antigen Receptor T) cells, TIL (Tumor Infiltrating Lymphocytes) and Tregs (Regulatory T cells) also known as suppressor T cells. Modulation of the microbiome composition to improve the efficacy of immunotherapies may also include the use of immune checkpoint inhibitors well known in the art such as, without limitation, PD-1 (programmed cell death protein 1) inhibitor, PD-L1 (programmed death ligand 1) inhibitor and CTLA-4 (cytotoxic T lymphocyte associated protein 4).
Some bacteria of the microbiome can also secrete molecules that will affect the brain.
Therefore, a further object of the disclosure is a method for controlling the microbiome of a subject, comprising administering an effective amount of the pharmaceutical composition as disclosed herein in said subject.
In a particular embodiment, the disclosure also relates to a method for personalized treatment for an individual in need of treatment for a bacterial infection comprising: i) obtaining a biological sample from the individual and determining a group of bacterial DNA sequences from the sample; ii) based on the determining of the sequences, identifying one or more pathogenic bacterial strains or species that were in the sample; and iii) administering to the individual a pharmaceutical composition according to the disclosure capable of recognizing each pathogenic bacterial strain or species identified in the sample and to deliver the packaged plasmid.
Preferably, the biological sample comprises pathological and non-pathological bacterial species, and subsequent to administering the pharmaceutical or veterinary composition according to the disclosure to the individual, the amount of pathogenic bacteria on or in the individual are reduced, but the amount of non-pathogenic bacteria is not reduced.
In another particular embodiment, the disclosure concerns a pharmaceutical or veterinary composition according to the disclosure for use in order to improve the effectiveness of drugs. Indeed, some bacteria of the microbiome, without being pathogenic by themselves, are known to be able to metabolize drugs and to modify them in ineffective or harmful molecules.
In another particular embodiment, the disclosure concerns the in-situ bacterial production of any compound of interest, including therapeutic compound such as prophylactic and therapeutic vaccine for mammals. The compound of interest can be produced inside the targeted bacteria, secreted from the targeted bacteria or expressed on the surface of the targeted bacteria. In a more particular embodiment, an antigen is expressed on the surface of the targeted bacteria for prophylactic and/or therapeutic vaccination.
The present disclosure also relates to a non-therapeutic use of the bacterial delivery particles. For instance, the non-therapeutic use can be a cosmetic use or a use for improving the well-being of a subject, in particular a subject who does not suffer from a disease. Accordingly, the present disclosure also relates to a cosmetic composition or a non-therapeutic composition comprising the bacterial delivery particles if the disclosure.
EXAMPLE 1
The example below demonstrates that a significative portion of a lambda receptor binding protein (RBP), e.g. the stf protein, can be exchanged with a portion of a different RBP. More particularly, specific fusion positions in the lambda RBP have been identified which allow one to obtain a functional chimeric RBP. Specifically, the data demonstrate, in a non-limiting embodiment, that in the case of phagemids derived from bacteriophage lambda, modifying the side tail fiber protein results in an expanded host range. The addition of chimeric stf proteins to lambdoid phagemids, is demonstrated to be a very powerful approach to modify and increase their host range, and in some cases is more efficient than the modification of the gpJ gene. In addition, modification of the side tail fiber protein to encode depolymerase activities can dramatically increase the delivery efficiency. In some cases, the addition of this enzymatic activity allows for 100% delivery efficiency while the wild-type lambda phagemid showed no entry at all. These two approaches can be combined to generate phagemid variants with different specificities and delivery efficiencies to many strains of bacterial species.
Tests were conducted to determine whether the modification of the tail tip gene (gpJ) would have an impact in the host range of lambda phagemids. The lambda tail tip was modified to include the mutations described in [11] to generate OMPF-lambda. This phagemid should now use OmpF instead of LamB as a primary receptor in the cell surface. Next, the delivery efficiency was tested in a collection of E. coli strains that spans a variety of O and K serotypes, as shown in FIG. 1.
As can be seen in FIG. 1, using phagemids that recognize a different cell surface receptor has a minimal impact on efficiency delivery and host range. Only 3 strains show a marginal improvement in the number of colonies after treatment with the modified phagemid. This result may be due to the presence of a capsule around the majority of the cells that forms a physical barrier to the phagemids, thus rendering this approach unsuccessful. In view of these results, the lambda stf gene was modified to include enzymatic activities against bacterial capsules.
The sequence of lambda stf (SEQ ID NO: 1) is:
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRY
SMDVEYGQYSVILQVDGEPPSHAGTITVYEDSQPGTLNDFLCAMTEDDA
RPEVLRRLELMVEEVARNASVVAQSTADAKKSAGDASASAAQVAALVTD
ATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAAAAESSKNA
AATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEA
AKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASA
AADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKR
AEDIASAVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETN
RKAPLDSPALTGTPTAPTALRGTNNTQIANTAFVLAAIADVIDASPDAL
NTLNELAAALGNDPDFATTMTNALAGKQPKNATLTALAGLSTAKNKLPY
FAENDAASLTELTQVGRDILAKNSVADVLEYL GAGENSAFPAGAPIPWP
SDIVPSGYVLMQGQAFDKSAYPKLAVAYPSGVLPDMRGWTIKGKPASGR
AVLSQEQDGIKSHTHSASASGTDLGTKTTSSFDYGTKTTGSFDYGTKST
NNTGAHAHSLSGSTGAAGAHAHTSGLRMNSSGWSQYGTATITGSLSTVK
GTSTQGIAYLSKTDSQGSHSHSLSGTAVSAGAHAHTVGIGAHQHPVVIG
AHAHSFSIGSHGHTITVNAAGNAENTVKNIAFNYIVRLA
The bold and underlined sequence represents the part of the protein that was introduced in the T4 phage [47]. Experiments were conducted to investigate if it was possible to exchange the C-terminus of the lambda stf with a tail fiber from a different phage to yield chimeric side tail fibers with an enzymatic activity against encapsulated E. coli. The tail fiber from the K1F phage which has been studied in depth and its structure solved [19], [20] was chosen. K1F encodes an enzyme with endosialidase activity, which is active against polymer of sialic acid secreted by K1-encapsulated E. coli. In fact, K1+ strains are immune to T7 infection because the capsule forms a physical barrier that prevents attachment of the phage, but if purified K1F enzyme is added to the cells before infection, T7 is able to lyse them [21], confirming that the presence of bacterial capsules is a powerful mechanism to avoid recognition by bacteriophages. Thus, by testing delivery of modified lambda-stf-K1 phagemids in K1+ strains it was possible to verify whether the lambda-stf chimeric proteins retain its enzymatic activity.
The sequence of K1F tail fiber (SEQ ID NO: 121)
is:
MSTITQFPSGNTQYRIEFDYLARTFVVVTLVNSSNPTLNRVLEVGRDYR
FLNPTMIEMLVDQSGFDIVRIHRQTGTDLVVDFRNGSVLTASDLTTAEL
QAIHIAEEGRDQTVDLAKEYADAAGSSAGNAKDSEDEARRIAESIRAAG
LIGYMTRRSFEKGYNVTTWSEVLLWEEDGDYYRWDGTLPKNVPAGSTPE
TSGGIGLGAWVSVGDAALRSQISNPEGAILYPELHRARWLDEKDARGW G
AKGDGVTDDTAALTSALNDTPVGQKINGNGKTYKVTSLPDISRFINTRF
VYERIPGQPLYYASEEFVQGELFKITDTPYYNAWPQDKAFVYENVIYAP
YMGSDRHGVSRLHVSWVKSGDDGQTWSTPEWLTDLHPDYPTVNYHCMSM
GVCRNRLFAMIETRTLAKNALTNCALWDRPMSRSLHLTGGITKAANQRY
ATIHVPDHGLFVGDFVNFSNSAVTGVSGDMTVATVIDKDNFTVLTPNQQ
TSDLNNAGKNWHMGTSFHKSPWRKTDLGLIPSVTEVHSFATIDNNGFAM
GYHQGDVAPREVGLFYFPDAFNSPSNYVRRQIPSEYEPDASEPCIKYYD
GVLYLITRGTRGDRLGSSLHRSRDIGQTWESLRFPHNVHHTTLPFAKVG
DDLIMFGSERAENEWEAGAPDDRYKASYPRTFYARLNVNNWNADDIEWV
NITDQIYQGGIVNSGVGVGSVVVKDNYIYYMFGGEDHFNPWTYGDNSAK
DPFKSDGHPSDLYCYKMKIGPDNRVSRDFRYGAVPNRAVPVFFDTNGVR
TVPAPMEFTGDLGLGHVTIRASTSSNIRSEVLMEGEYGFIGKSIPTDNP
AGQRIIFCGGEGTSSTTGAQITLYGANNTDSRRIVYNGDEHLFQSADVK
PYNDNVTALGGPSNRFTTAYLGSNPIVTSNGERKTEPVVFDDAFLDAWG
DVHYIMYQWLDAVQLKGNDARIHFGVIAQQIRDVFIAHGLMDENSTNCR
YAVLCYDKYPRMTDTVFSHNEIVEHTDEEGNVTTTEEPVYTEVVIHEEG
EEWGVRPDGIFFAEAAYQRRKLERIEARLSALEQK
The bold and underlined sequence represents the part of the protein that has been crystalized and has been shown to retain its endosialidase activity. Since there is no identity between the lambda stf protein and the K1F tail fiber, the insertion point was made based on conclusions extracted from different sources of information, including literature and crystal structures.
The stf gene was modified to include the K1F endosialidase at its C-terminus using a Cas9-mediated gene exchange protocol [22]. lambda-K1F phagemids were produced as in [23] and titrated against some K1+ strains, specifically E. coli UTI89 and S88. The results were striking; in these strains, there is no delivery if lambda wild-type stf is used, but the addition of the K1F variant gives 100% delivery (FIG. 2).
The same principle was followed to create a different variant of lambda-stf, this time with K5-capsule degrading activity (K5 lyase tail fiber from phage K5A). As in the case of K1F, there is no homology between lambda-stf and K5 lyase, but its crystal structure has been published [24]. Hence, the same approach as for K1F was used to generate stf-K5 chimeric side tail fibers and tested the produced phagemids against a K5-encapsulated strain of E. coli (ECOR 55). In this case, however, a delta-stf lambda production strain was produced with the stf fusion gene expressed in trans under the control of an inducible promoter. As depicted in FIG. 3, there was some residual delivery using the wild-type lambda-stf, probably due to the presence of some cells with a thinner K5 capsule. However, the addition of lambda-stf-K5 chimeras allows for an improvement in delivery of more than 106 fold.
In some other cases, side tail fibers can be found that have some degree of homology to lambda stf, although no crystal structure is available. In these cases, the insertion point was designed as the last stretch of amino acids with identity to lambda stf. For example, in two in-house sequenced phages, the predicted side tail fiber proteins are as follows:
Phage AG22 stf
(SEQ ID NO: 262)
MAIYRQGQASMDAQGYVTGYGTKWREQLTLIRPGATIFFLAQPLQAAVI
TEVISDTSIRAITTGGAVVQKTNYLILLHDSLTVDGLAQDVAETLRYYQ
GKESEFAGFIEIIKDFDWDKLQKIQEDVKTNADAAAASQQAAKTSENNA
KTSATNAANSKKGADTAKAAAESARDAANTAKTGAEAAKSGAESARDAA
NTAKAGAESARDQAEEYAKQAAEPYKDLLQPLPDVWIPFNDSLDMITGF
SPSYKKIVIGDDEITMPGDKIVKFKRASTATYINKSGVLTNAAIDEPRF
EKDGLLIEGQRTNLLINSTNPSKWNKSSNIVIILDRSGVDDFGFQYAKF
TLKPEMVGQTSSINIVTVSGSRGFDVTGNEKYVTISCRAQSGTPNLRCR
LRFENYDGSAYASLGDAYVNLTDLSIEKTGGAANRITARAVKDEASKWI
FFEATIKALDTENIVIIGAMVQYAPAKDGGGTGADDYIYIATPQVEGGV
CASSFIITEATPVTRASDMVTIPIKNNLYNLPFTVLCEVHKNWYITPNA
APRVFDTGGHQSGAAIILAFGSADGDNDGFPYCDIGKSNRRVNENAKLK
KMIIGMRVKSDYNTCCVSNARISSETKTEWRYIVSTATIRIGGQTSTGE
RHLFGHVRNFRIWHKALTDHQLGEIV
Its alignment to lambda stf is as follows:
Lambda 156 STSAGQAASSAQEASSGAEAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQ
AG22  92 ETLRYYQGKESEFAGFIEIIKDFDWDKLQKIQEDVKTNADAAAASQQAAKTSENNAKTSA
 *           *               *          *** *  ****** **  *
The sequence of the stf of a second in-house phage is as follows:
Phage SIEA11 stf
(SEQ ID NO: 263)
MSTKFKTVITTAGAAKLAAATVPGGKKVTLSAMAVGDGNGKLPVPDAGQ
TKLVREVWRHALNKVSVDNKNKNYIVAELVVPPEVGGFWMRELGLYDDA
GTLIAVSNMAESYKPELAEGSGRAQTCRMVIIVSNVASVELSIDASTVM
ATQDYVDDKIAEHEQSRRHPDATLTEKGFTQLSSATNSTSESLAATPKA
VKAANDNANSRLAKNQNGADIQDKSAFLDNVGVTSLTFMKNNGEMPVDA
DLNTFGSVKAYSGIWSKATSTNATLEKNFPEDNAVGVLEVFTGGNFAGT
QRYTTRDGNLYIRKLIGTWNGNDGPWGAWRHVQAVTRALSTTIDLNSLG
GAEHLGLWRNSSSAIASFERHYPEQGGDAQGILEIFEGGLYGRTQRYTT
RNGTMYIRGLTAKWDAENPQWEDWNQIGYQTSSTFYEDDLDDLMSPGIY
SVTGKATHTPIQGQSGFLEVIRRKDGVYVLQRYTTTGTSAATKDRLYER
VFLGGSFNAWGEWRQIYNSNSLPLELGIGGAVAKLTSLDWQTYDFVPGS
LITVRLDNMTNIPDGMDWGVIDGNLINISVGPSDDSGSGRSMHVWRSTV
SKANYRFFMVRISGNPGSRTITTRRVPIIDEAQTWGAKQTFSAGLSGEL
SGNAATATKLKTARKINNVSFDGTSDINLTPKNIGAFASGKTGDTVAND
KAVGWNWSSGAYNATIGGASTLILHFNIGEGSCPAAQFRVNYKNGGIFY
RSARDGYGFEADWSEFYTTTRKPTAGDVGALPLSGGQLNGALGIGTSSA
LGGNSIVLGDNDTGFKQNGDGNLDVYANSVHVMRFVSGSVQSNKTINIT
GRVNPSDYGNFDSRYVRDVRLGTRVVQTMQKGVMYEKAGHVITGLGIVG
EVDGDDPAVFRPIQKYINGTWYNVAQV
Its alignment to lambda stf is as follows:
Lambda 367 SSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTAPTALRGTNNTQIANTAFV
SIEA11 180 SSATNSTSESLAATPKAVKAANDNANSRL---AKNQNGADIQDKSAF-LDNVGVTSLTFM
********* *********   *  *           *            *       *
In these two specific cases, it was unknown which antigen these side tail fibers were able to recognize, so lambda packaged phagemids with the chimeric side tail fibers were produced and their delivery efficiency was tested in a E. coli collection that contains a very diverse group of O and K serotypes.
As shown in FIG. 4, the addition of a chimeric stf allows the lambda-based phagemid to show increased delivery efficiency in 25 out of 96 strains tested (more than 25% of the collection). In some cases, the increase is modest; in others, it allows for very good delivery efficiency in strains that had no or very low entry with wild-type lambda phagemids. It is also worth noting that AG22 belongs to the Siphovirus_family, like lambda, but SIEA11 is a P2-like phage. This highlights the significant observation that stf modules can be exchanged across bacteriophage genera.
Other side tail fiber genes have been analyzed as shown in FIG. 4 and several insertion points into the lambda stf gene have been identified that give chimeric variants with differential entry in the E. coli collection as shown previously. These insertion points are based on the results for the non-homologous tail fiber variants (such as in the cases for K1F and K5 above) or on varying degrees of homology between lambda stf and the variant to be tested. This homology can be short, about 5-10 aminoacids, or substantially similar. The insertion points tested are shown in bold and underlined below:
Lambda stf
(SEQ ID NO: 1)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQST A
DAKKS AGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAAAA
ESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSETNASSS
AGRAASSATAAENSARAAKTSETNARSSETAAER SASAAA DAKTAAAGSASTASTKATEAAGSAV
SASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVV
MDETNR KAPLDSPALTGTPTAPTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALG
NDPDFATTMTNALAGKQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVA
DVLEYL GAGENS AFPAGAPIPWPSDIVPSGYVLMQGQAFDKSAYPKLAVAYPSGVLPDMRGWTIK
GKPASGRAVLSQEQDGIKSHTHSASASGTDLGTKTTSSFDYGTKTTGSFDYGTKSTNNTGAHAHSL
SGSTGAAGAHAHTSGLRMNSSGWSQYGTATITGSLSTVKGTSTQGIAYLSKTDSQGSHSHSLSGTA
VSAGAHAHTVGIGAHQHPVVIGAHAHSFSIGSHGHTITVNAAGNAENTVKNIAFNYIVRLA
The lambda stf protein consists of 774 aminoacids. The insertion points can be found closer to the N-terminus (amino acid 131, insertion point ADAKKS (SEQ ID NO: 249)) or closer to the C-terminus (amino acid 529, insertion point GAGENS (SEQ ID NO: 252)). FIG. 5 depicts some selected examples for the insertion points ADAKKS (SEQ ID NO: 249), SASAAA (SEQ ID NO: 251) and MDETNR (SEQ ID NO: 250).
The results described herein show that it is possible to build chimeric tail fibers that combine the part of one tail fiber that attaches to the capsid of one phage (usually the N-terminus of the protein) with the part of another fiber that interacts with the bacterium (usually the C-terminus of the protein). Stretches of homology between the sequence of different tail fibers can be considered as preferable recombination points. In order to identify such points for the stf protein of phage lambda a scan of the stf sequence was performed with a 50aa window and a phmmer search [25] was performed on each window to identify homologous sequences in the representative proteome 75 database (FIG. 6).
EXAMPLE 2
T4-like phages are a very diverse family of bacteriophages that share a common long tail fiber architecture: a proximal tail fiber that attaches to the phage particle and a distal tail fiber (DTF) that encodes host specificity linked by proteins acting as “hinge connectors” (Desplats and Krisch, 2003, Res. Microbiol. 154:259-267; Bartual et al. 2010, Proc. Natl. Acad. Sci. 107: 20287-20292). It is thought that the main host range determinants of the tail fiber reside in the distal part. Hence, it is very important to understand if it is possible to translate the host range of a given T4-like phage, which are known to be very broad, to any other phage or phagemid of interest. The distal tail fiber (C-terminal domain of the T4-like long tail fiber) of several T4-like phages were screened for possible functional insertion sites, several fusions with the Lambda stf gene were generated and their host range screened.
Possible insertion sites in the DTF that, when fused to a heterologous tail fiber (the lambda phage stf), will give a functional chimera were searched. The DTF of the phage (WW13) was used as a testbed. This phage possesses a classical T4-like architecture, with a proximal and a distal tail fiber separated by hinge connectors, a gp38 chaperone/adhesin (to assist folding of the tail fiber and recognition of the host (Trojet et al., 2011, Genome Biol. Evol. 3:674-686) and a gp57A chaperone known to be needed for proper folding of the tail fiber (Matsui et al., 1997, J. Bacteriol. 179:1846-1851). Since the endogenous genomic regulation of T4-like phages is complex and may include unknown layers of regulation (Miller et al., 2003, Microbio. Mol. Biol. Rev. 67:86-156), a synthetic linker encoding a RBS was designed to replace the natural DNA linker between the DTF gene and the adhesin; immediately downstream, another synthetic RBS preceding the chaperone gp57A was added, hence creating a polycistronic mRNA encoding for all the functions needed for the proper folding of the DTF (FIG. 7). This construct was built in a plasmid under the control of an inducible promoter and complemented in trans in a strain producing lambda-based phagemids.
FIG. 7. depicts the architecture of an engineered lambda stf-T4-like DTF chimera. The semicircles denote RBS sites; the T sign, a transcriptional terminator; the arrow, a promoter. Several parts of the C-terminus of the DTF were screened and fused to the lambda stf gene at the GAGENS (SEQ ID NO: 252) insertion site. Several variants of the chimera lambda stf-WW13 were functional, as assessed by production of phagemid particles and transduction of a chloramphenicol marker in a collection of E. coli strains. The functional chimeras shown in FIG. 8 were obtained with fusion at the IIQLED (SEQ ID NO: 254) insertion site in WW13. Additional functional chimeras were obtained by fusion at the lambda stf MDETNR (SEQ ID NO: 250) insertion site and at the WW13 DTF GNIIDL (SEQ ID NO: 255), VDRAV (SEQ ID NO: 261) and IIQLED (SEQ ID NO: 254) insertion sites (FIG. 11).Other T4-like phages, like PP-1, sharing sequence homology with WW13 were also tested and verified to produce functional chimeras (FIG. 8). These functional chimeras show a IATRV insertion site at the beginning of PP-1 DTF part.
FIG. 8 depicts screening of phagemid particles with chimeric lambda stf-T4-like DTFs. A collection of 96 different wild type E. coli strains, encompassing different serotypes, was transduced with lambda-based phagemids and plated on Cm LB agar. Left panel represents wild-type lambda stf; the middle panel represents chimeric lambda-stf-WW13; and the right panel, represents chimeric lambda-stf-PP-1.
The insertion sites found for WW13 do not always exist in a given T4-like DTF, thereby complicating the analysis. Another functional insertion site without homology to WW13 was discovered for a second phage (WW55, FIG. 9). The same TPGEL insertion site could be found in a subset of T4-like phages and proven to yield functional chimeras with at least one of them, WW34 (FIG. 9), and at MDETNR (SEQ ID NO: 250) insertion site in lambda stf.
FIG. 9. shows screening of phagemid particles with chimeric lambda stf-T4-like DTFs. A collection of 96 different wild type E. coli strains, encompassing different serotypes, was transduced with lambda-based phagemids and plated on Cm LB agar. The left panel represents wild-type lambda stf; the middle panel represents chimeric lambda-stf-WW55; and the right panel represents chimeric lambda-stf-WW34.
Since T4-like DTF proteins may or may not share common sites for insertion, attempts were made to identify a universal insertion site that exists in all T4-like DTFs. When several T4-like DTFs are aligned, no homology along the whole DTF gene present in all the sequences exists, except for the N-terminus which is well conserved. The N-terminus of the DTF is thought to interact with the hinge connectors for attachment to the main phage particle.
Although the classic view is that the host range determinants reside in the C-terminal part of the DTF, recent studies have proven that the N-terminus may also be involved in this process (Chen et al., 2017, Appl. Environ. Microbiol. Vl. 83 No. 23). The N-terminus of the DTF was then scanned to look for an insertion site that exists in all T4-like phages and that is able to yield functional chimeras. Phage WW13 DTF and insertion site MDETNR (SEQ ID NO: 250) in lambda stf were used. While the direct fusion of the complete DTF gene (starting at amino acid 2) gives particles with some activity, a region from amino acid 1 to 90, with a preferred region from amino acid 40 to 50 of the DTF, that recapitulates the behavior of the DTF fusion was identified and is shown in FIG. 10. Importantly, this region exists in all T4-like phages screened and could be very rapidly used to generate chimeras with a diverse set of DTFs, including WW55 (FIG. 10).
Accordingly, the present disclosure is useful for the generation of phage and phagemid particles with altered host ranges, since it provides a practical framework for the construction of chimeras using the DTFs from any T4-like phage, highlighting its modularity and translatability.
EXAMPLE 3
The human microbiome comprises different zones of the body, including gut, skin, vagina and mouth [29]. The microbiota in these areas is composed of different communities of microorganisms, such as bacteria, archaea and fungi [29]-[31]. While numerous studies have been made that try to elucidate the specific composition of these communities, it is becoming clear that while there may exist a “core microbiome”, there are many variations in the relative content of each microorganism depending on several factors, such as geographical location, diet or age [32]-[35].
Specifically, in the case of the human gut microbiota, it is not possible to know a priori what are the bacterial species that a given person possesses without running a diagnostic method. In the case of Escherichia coli, some studies have been made that point out to the prevalence of some serotypes and phylogenetic groups in the majority of humans; however, there are significant changes in the composition of the samples depending on the geographic distribution as well as the time of sampling: for example, samples isolated from Europe, Africa, Asia and South America in the 1980s show a prevalence for phylogroups A and B1 (55% and 21%, respectively); but samples obtained in the 2000s in Europe, North America, Asia and Australia belong mainly to the B2 group (43%), followed by the A (24%), D (21%), and B1 (12%) [36]. It is also thought that phylogenetic groups B2 and D are usually more commonly associated with pathogenic strains than with commensal strains [37], but there are studies showing a number of human- and non-human-specific strains belonging to phylogenetic group B2 that are commensals and belong to different serotypes [38].
The intrinsic variability of the human microbiome, and specifically that of Escherichia coli subtypes, makes it difficult to design targeted therapeutic approaches. In the case of phage therapy aimed at killing a target bacterial population, for instance, two possible approaches are possible: first, the use of narrow host range particles that are able to recognize and target a specific E. coli serotype or second the use of broad host range phages that are able to recognize many different strains, sometimes even from different genera [39]. This difficulty is exacerbated if one takes into account strategies that do not aim to kill the target bacterial population, but that seek to add a function to them (i.e. delivery of a factor that will have an effect in the host and that will be expressed by the targeted microbiota). In this specific case, the use of packaged phagemids is of great interest, since they do not kill the host (unless their payload carries genes aimed at killing the host), payload does not replicate and expand and does not contain any endogenous phage genes. However, as in the case of phages, a diagnostic study would be needed to identify the specific serotypes/variants of bacteria that exist in the patient before the treatment in order to find or design a packaged phagemid that allows for delivery of a payload adding a function to the target bacteria without killing them.
By combining these two approaches, it was proposed to use engineered delivery vehicles that are able to recognize a large number of strains belonging to different serotypes and phylogenetic groups (i.e., engineered particles having a “broad host range”), with a focus on Escherichia coli. As opposed to a killing-oriented approach, where the targeted bacterial population needs to be as close as possible to 100% to reduce their numbers, a therapeutic delivery approach does not need a priori to reach a large percentage of bacteria; the delivery needs to be high enough for the therapeutic payload to be expressed at the correct levels, which may be highly variable depending on the application. Additionally, the payload can be expressed by different serotypes or phylogenetic groups. This approach increases the chance that the particle will deliver a payload expressed in vivo in the majority of patients.
To achieve the delivery in bacterial communities composed of unknown serotypes/variants of target strains, delivery vehicles were engineered to contain chimeric side tail fibers (stf) that have been selected due to their ability to recognize a large variety of target strains. There are many phages that have been described as having a broad host range in E. coli and many of these belong to the T4 family, although in general, phages against E. coli and related bacteria have a restricted host range.
However, according to [41], there is no consensus as to how many strains need to be targeted by a phage to be considered as a “broad host range”.
In the case of Escherichia coli, the ECOR collection is a set of strains isolated from different sources that is thought to represent the variability of this bacterium in Nature [42]. Some phage have been shown to have a broad host range against this collection (for instance, about 53% of the ECOR strains can be lysed with phage AR1 [43] and about 60% with phage SU16 [44]). As opposed to this, a single phage is able to infect 95% of Staphylococcus aureus strains [40].
It was decided to use human strains of this collection to test engineered delivery vehicles with chimeric stf and assess their host range in an attempt to identify variants that are able to recognize as many hosts as possible, as has been described in the literature [45]. The difference is that the present assays measure delivery efficiency as opposed to lysis.
Strains from an overnight culture were diluted 1:100 in 600 uL of LB supplemented with 5 mM CaCl2 in deep 96 well plates and grown for 2 hours at 37° C. at 900 rpm. 10 uL of packaged phagemids produced at an average of 106/uL were then added to 90 uL of the bacterial cultures, incubated 30 minutes at 37° C. and 10 uL of the mixtures plated on LB agar supplemented with 24 ug/mL chloramphenicol and incubated overnight at 37° C. The next day, the density of the dots was scored from 0 to 5, with 0 being no transductants and 5 being a spot with very high density [FIG. 11]. The density of the spots is directly related to the delivery efficiency of the packaged phagemids, since it corresponds to the number of bacteria that have received a payload containing a chloramphenicol acetyltransferase gene.
Several stf chimeras were tested and screened in 40 human strains of the ECOR collection. As a control, the delivery efficiency of the wild-type stf was tested. The packaged phagemid variant used for the delivery experiments was modified so that its tail tip gpJ now recognizes a receptor other than LamB (1A2 variant)(SEQ ID NO: 214). In FIG. 12, the raw dot titrations for 18 stf are shown and in FIG. 13 a bar-formatted table is shown with the delivery efficiencies scored by dot density as well as the delivery statistics.
Taking only into account dots with density scores of 3 and higher (considered as medium to high delivery efficiency), some stf s can be considered as broad host range because the delivery efficiency in the selected ECOR strains is significantly higher than when using the wild type stf. For example, for stf EB6 or stf 68B, about 50% of the strains show medium to high delivery efficiencies, as compared to 17.5% of the strains with the wild type stf. These stf are good candidates for in vivo delivery, since they are able to deliver in different phylogenetic groups as well as serotypes. At the bottom of the Table in FIG. 13, a bar-formatted representation for density scores higher than 3 is shown, where the threshold for a broad host range stf is set at an increase of at least 2× compared to the basal line of the wild type stf; this is, stf that are able to deliver with scores of 3 and higher in at least 35% of the strains. Other stf also show an increased delivery as compared to the wild type stf, so a less stringent threshold was set for stf able to deliver with scores 3 or higher with at least a 50% increase compared to the number of strains delivered with the wild-type stf (this is, delivery with scores of 3 and higher in at least 26.25% of the strains). As a comparison, data for stf K1 and stf 66D is shown: these stf seem to be delivering efficiently in a small number of strains (for instance, strains B and AB for stf K1; and strains E and AF for stf 66D), which means that they probably have a narrow host range; this is to be expected, since in the case of the K1 stf the cognate receptor is the K1 capsule [46]. Additionally, data are shown for a chimera with a stf originating in a T4-like phage; as the literature suggests, this chimera shows a broad host range although it does not seem to be the best candidate.
Taken together, these results suggest that the stf of a delivery vehicle can be engineered to recognize a wide number of target E. coli strains, hence rendering it “broad host range”. This type of particles can be very useful to deliver payloads adding a function to the target bacteria without having to engineer a specific variant that recognizes a given bacterial strain.
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SEQUENCES
1) INSERTION POINT ADAKKS
STF-25 (SEQ ID NO: 2)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSETAAASSRNAAKTSETNAGNSAKAAASSKTAAQNAATAAERSE
TNARASEEASADSEEASRRNAESAAENAGVATTKAREAAADATKAGQKKDEALSAAT
RAEKAADRAEAAAEVTAEPCANIVPPLPDVWIPFNDSLDMIAGFSPGYKKIAIGDDVVQ
VASDKQVNFSRASTATYINKSGELKTAEINEPRFECDGLLIEGQRTNYMLNSESPASWGK
SSNMDVPETGTDSFGFTYGKFVCNDSLVGQTSAINMASIAATKSVDVSGDNKYVTTSCR
FKTERQVRLRIRFDKYDGSATTFLGDAYIDTQTLEISMTGGAAGRITARVRKDKTTGWIF
AEATIQAIDGELKIGSQIQYSPGQGGATVSGDYIYLATPQVENGPCVSSFIISGGSATTRAS
DLVSIPTRNNLYKLPFTFLLEIHKNWDIAPNAAPRVWDIAAANTGQSAIAAINRGSGKLY
MSLSNPSGSYVNSAATDVFAEKTTFGCIAKADGHFHVVTNGKAVNEVYCEYNGVTAD
KNIRFGGQTNTGERHLFGHIRNFRIWHKELNDRQLKEVV
STF25-AP1 (SEQ ID NO: 3)
MKDLTLKFHDKLQFKAFLSSLGWAEDEDLQNKLLVDEIGFTYTETGVTEEGEPVCIRND
GYFVNIRILDDLFDVSVFSDYVVELETPLREWS
STF-27(SEQ ID NO: 4)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSETAAASSKNAAKTSETNAANSAQAAAASQTASANSATAAKKSE
TSAKNSETATKASEKNAKSSQTAAKTSETNAKDSEANAKVSETAAANSAKASAASQTA
AKASEDAAREYANQTAEPYRYVLQPLPDVWIPFNDSLDMITGYSPGYKKVKIGDNVVQ
VASDKQVNFSRASTATYINKSGELKTAEINEPRFECDGLLIEGQRTNFFQNSTDPSKWNK
STSLDVTETGTDSFGFNYGRFVVQDSIVGTSKAHTIIGLYSSTGGVDTSGDEKHVTISCRV
KSEVDNIAVRILFEHYDGEVRTSIGAANLNLTTRIISKTGQTSRVTARSVKDDATGWIFFE
ATLKADTTENTVGGFVQYSPDTGQMVTSGDYLDVTTPQIEAGTGASSFIVTGTAPATRA
SDMVTVPIKNNLYNLPFTVLCEVHKNWYKTPNVAPRVFDTGGHQTGAGIVMGFGSSGG
YDGFPYCDIGGSDRRINENAGLEKMLIGMRVKSERSTCVVSNGKLSSETKTKWEYIRST
ATIRIGGQTTAGLRHLFGHVRNFRLWHKELTDAQLGEVVE
STF27-AP1 (SEQ ID NO: 5)
VRDFTLRFSDKADFRAFLRKLNWEEDEELQNAVLVDEIGFTFRETDVSDDGEPEYTRNE
GYFVNIRLLDDGFEDSVFREWVVTPERPLREWF
STF27-AP2 (SEQ ID NO: 6)
MLPQHSDIEIAWYASIQQEPNGWKTVTTQFYIQEFSEYIAPLQDAVDLEIATEEERSLLEA
WNKYRVLLNRVDTSTAPDIEWPTSPAE
>STF-28 (SEQ ID NO: 7)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSETAAASSRNAAKTSETNAGNSAKAAASSKTAAQNAATAAERSE
TNARASEEASADSEEASRRNAESAAENAGVATTKAREAAADATKAGQKKDEALSAAT
RAEKAADRAESAAEVTAEPCANIVPPLPDVWIPFNDSLDMITGFSPSYKKIVIGDDEITMP
GDKIVKFKRASTATYINKSGQLKLAEVDEPRFERDGLLIEGQRTNYLRNSNKPDSWTVH
SALNKTFGTDKQGFNYATVTPTESIVGTTGGYTVHGVVAADRFPLASGECFTFSCRVKG
AKARCRLRVSVIIGGTDTFSADSYLDLDTRIATVSGNTSLITAKAEQQGEWTYYEATYTA
NTDIDTVNCAFYMTNKISNEPFYDDSTLTMTTPQIELGNTASSFIVTTMPTTRASDVVTIP
SANNLSTRPFTVLCEVRRNWSTPPNVAPRIFDVGGHSIDDNYLSLGFVSTGKISANVGMV
QPQISSDGERFIVGVRAKSDLSVNAICNGNYTTNLNGKIFGVTATSYRFGGQTAAGTRHL
FGHIRNFRVWFKELNDRQIKEAV
STF28-AP1 (SEQ ID NO: 8)
MKDLTLKFPGNREFKSFLSSLDWEEDEDLQNKLLVDEIGFTYTETGVTEEGEPVCIRNNG
YFVNIRILDDLFDVSVFSDYVVELETPLREWS
2) INSERTION POINT SASAAA
STF-15 (SEQ ID NO: 9)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAAASATASANSQKAAKTSETNAKVSETAAANSAKASAASQTAAKASEDAAREY
ASQAAEPYKYVLQPLPDVWIPFNDSLDMITGFSPSYKKIVIGDDEITMPGDKVVKFKRAS
TATYINKSGVFSVAKIDEPRFEKEGLLIEGQRTNYFVKSNTPAEWTSTSNIDKTNNGVDE
FGFSYAKMRTKDNMTGQSSALSLHRCSASRGIDVSGDNKYCTVSCRVKAPDGLRCRLR
FEKYDGSVYTFLGDAYLTFGTLIIEKTGGAANRIAATATKDPVTGWIFYEATIEAVEGET
LIGAMIQYAPKKGGITEAGDYIYLATPQFENGGCASSFVITTTAPATRSSDMVTIPTKNNI
YNRPLTCLVEVNRIWGDIPPNVAPRIFDFSGVPPIESITYAFNTTEKYYGQLYMQTYKAST
STYVSSVFAGRADVRKFIGGFNIYSDGTKRVVSNGEATKTMKTEWTGVKTRTFIRIGGQ
ATSGTRHLFGHLRNLRLWHKELTDAQMGESIK
STF15-AP1 (SEQ ID NO: 10)
MKDLTLKFADRADFSAFMESIGYYDDESMQDDILIDVIGNVYKETGELTEDGEPACVKE
DGYFVNVRIINDSQISSLFDEHAVAVEHQLRSWM
STF15-AP2 (SEQ ID NO: 11)
MATSTVIPDDIKTLKGDVSKAKEDISSINVKVSTLQTDMDSAKQDISTRYTKTEVDNKLK
NKVEVNDLESGRYGGDFYPLTGREAFYLWGLGTTTAAANLYLNPDPAISSVLRSTSSIR
YKHSVETIDSEHADLIFRMRPVWYRSQCENDRRDWGFYGLIAEEVGEIAPQFVHWRPA
NEDDAPETISSNGLVAEGVMYERLVVPLIHHIQKLTERVDELESELKLLSTSQSDIG
STF-16 (SEQ ID NO: 12)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAAASATASANSQKAAKTSETNAKTSETAAANSAKASAASQTAAKASEDAAREYA
SQAADPYKYVLQPLPDVWIPFNDSLDMITGFSPSYKKIVIGDDEITMPGDKIVKFKRASK
ATYINKSGVLTEAAIDEPRFERDGLLIEGQRTNLLLNSTNPSKWNKSGNLELTEISTDSFN
FTYGRFTVKDTLIGQTSAINIVTISGSKGFDVTGDEKYVTISCRVRSDVENIRCRLRFEHH
DGYTYTFLGDAYLNLSTLVIDKTGTAADRIIAKAVKDEVTGWIFYQATINALDTESMIGA
MVQYAPVKGSGTASGDYLDIATPQVEGGSSASSFIVTDITASTRASDMVTVPIKNNLYNL
PFTVLCEVHKNWYKTPNAAPRVFDTGGHQTGAAIILGFGRSTDYDGFPYCDIGLANRRV
NENASLEKMVMGMRVKSDQSTCSVSNGRISSEKKATWSYIQNSAIIRIGGQTTAGLRHL
FGHVRNFRIWHKALTDAQMGESI
STF16-AP1 (SEQ ID NO: 13)
MKDLTLKFADRADFSAFMDSIGYYDDESMQDDILIDVIGNVYKETGELTEDGEPVCVKE
DGYYVNVRIINDAKKSSIFDEYAVVVEHQLRGWM
STF16-AP2 (SEQ ID NO: 14)
MATSTVIPGDITTLKGDVSKAKEDISSINGKVSTLQADMTSAKQDISTRYTKTEVDNKLK
NKLEVNALESGRYGGDFYPLTGREAFYLWGLGTTTAAANLYLNPDPAISSVLRSTSSIRY
KHSVETIDSEHADLIFRMRPVWYRSQCENDRRDWGFYGLIAEEVGEIAPQFVHWRPANE
DDAPEAISSNGLVAEGVMYERLVVPLIHHIQKLTERVDELESELKLLSVSRSDIG
STF-17 (SEQ ID NO: 15)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAAGSKTAAALSASAASTSAGQASASATAAGKSAESAASSASTATTKAGKATEQA
TAAARSASAAKTSETNAKTSADNAASSKAAAASSASSAASSASSASASKDEATRQASAA
KGSATTASTKATEAAGSATAAAQSKSTAESAATRAETAAKRAEDIASAVALEDASTTKK
GIVQLSSATNSTSESLAATPKAVKAVMGETNKKAPLNSPALTGTPTTPTARQGTNNTQIA
STAYVMAAIAALVDSSPDALNTLNELAAALGNDPNFATTMTSALAGKQPKDATLTALA
GLATAADRFPYFTGNDVASLATLTKVGRDILAKSTVAAVIEYLGLRELGTSGEKIPLLST
ANTWTNRQTFSGGLSGELSGNASTAAKLKTARKISNVAFDGSSDITLKASHVGAFALGK
TGSTVANDKAVGWNWSSGAYNATISGASTLIIHFYMGEGSCPAAQFRINYKNGGIFYRS
ARDGYGFEADWSEFYTTTRKPSAGDVGALPLSGGQLNGALGIGTSSALGGNSIVLGDND
TGFKQNGDGNLDVYANNVHVMRFVSGSIQSNKTINITGRVNPSDYGNFDSRYVKDVRL
GSQQYYGVNNWQTWNFQCPSGHVLSGINVQDTGSNSADNIAGVYYRPVQKYINGTWY
NVASV
STF17-AP1 (SEQ ID NO: 16)
MMHLKNIKAGNAKTLEQYELTKKHGVIWLYSEDGKNWYEEVKNFQPDTIKIVYDENNI
IVAITKDASTLNPEGYSVVEIPDITANRRADDSGKWMFKDGAVIKRVYTEEELRLQTENQ
KKILLQQAREKTQFWQTQLTLGIITDSDRQQLMNWMRYVQQVETTDTSVLPVTFPEPPE
STF-13 (SEQ ID NO: 17)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAASSATASANSQKAAKTSETNAKASETAAANSAKASAASQTAAKASEDAAREYA
SQAAEPYKQVLQPLPDVWIPFNDSLDMLAGFSPGYKQITVGDDVIKMPSDKVVSFKRAS
GATYINKSGVLTVAEVDEPRFEREGLLIEGQRTNYHLNSLTPSKWGATTSVTITESGVDE
FGFTYGRFQIKDEKIGTNTTMNIAAVSGGRGVDVTGTEKYVTTSCRVKSDSANIQCRIRF
ERYDGSAYFYLADAYLNITDMSIRKTGGGAARITARAEKESNGWIYFEVTYQSEAIDNIVI
VGSQIQIAPPVSPGTYLGGEYLDVTTPQFEGGSCASSFIISDTVASTRASDIVTLPCKNNM
ASKPLTCMVEVNKNWSIAPNSAPRIYDITGFKTKDDAFVFAFRNTAGSVGTPYVQFGNPI
SFPPGNYPRKIIAVYRIKSDGKFQAGCNGVLSTPASTTWKSVSGATGIRTGGQTTAGLRH
LFGYIRNFRIWHKELTDAQMGEII
STF13-AP1 (SEQ ID NO: 18)
MRDLIIKFTDKADFSAFMKSAGYYDDESMQDDILIDVIGNVYKETGELTEDGEPVCVKE
DGYFVNVRIINDAKKSSIFDKYAVVVEHQLRGWM
STF13-AP2 (SEQ ID NO: 19)
MATSTVIPGDITKLKGDVSKAKEDISSISRKVSTLQTEMTSAKQDISSRYTKTEVDNKLK
NKVEVNDLESGRYGGDFYPLTGREAFYLWNLATTTAAANLYLNPDPAISSVLRSTSSIR
YKHSVETIDSEHADLIFRMRPVWYRSQCENDRRDWGFYGLIAEEVGEIAPQFVHWRPA
NEDDAPEAISSNGLVAEGVMYERLVVPLIHHIQKLTERVDELESELKLLLTSRSDIR
STF-12 (SEQ ID NO: 20)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAAASATASANSQKAAKTSETNAKTSETAAANSAQASAASQTAAKASEDAAREYA
SQAAEPYKYVLQPLPDVWIPFNDSLDMLAGFSPGYKQITVGDDVIKMPSDKVVSFKRAS
GATYINKSGVLTVAEVDEPRFEREGLLIEGQRTNYFRNSNTPEAWNNTGSVSVESFDSD
KGFNYGRITVINENPTAQGYQAIAVNTNDAYTCPAGSYTTISCLTKSDNSRCRARFGKM
SDNGAFVFHSDAVLDPVTGNVVHGNNVTVTAERVGEWWLFTATLFADAEMIISSRFEIL
AMPGISIIPNGSTLDTAMPQAEIGSYRTSFIITEGAPGTRSSDMVTIPVRNNIHRLPFSALVE
VNKNWDIPPSKSPLIFNVKDYQENGLFTHGFRGNNFSDAGSPFISMGGCNKYVATTQRK
IISGFRCGADGDVQAVCNGELSVAAKTTWTSIVPRAVLRIGGQGTNGEYHLFGHIRNLRI
WHKELTDAQMGESIK
STF12-AP1 (SEQ ID NO: 21)
MKDLTLKFADRADFSAFMESIGYYDDESMQDDILIDVIGNVYKETGELTEDGEPVCVKE
DGYFVNVRIINDVKKSSIFDKYAVVVEHQLRGWM
STF12-AP2 (SEQ ID NO: 22)
MATSTVIPGDITTLKGDVSKTKEDISSINGKVSTLQTDMTSAKQDISTRYTKTEVDNKLK
NKLEVNDLESGRYGGDFYPLTGREAFYMWGLGTTTAAANLYLNPDPAISSVLRSTSSIR
YKHSVETIDSEHADLIFRMRPVWYRSQCENDRRDWGFYGLIAEEVGEIAPQFVHWRPA
NEDDAPEAISSNGLVAEGVMYERLVVPLIHHIQKLTERVDELESELKLLSVSRSDIG
STF-63 (SEQ ID NO: 23)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAANSATAAKKSETNAKNSESAAKVSETNAKASENKAKEYLDKVGGLVSPMTQY
DWPVVTGNESFYIKIAKLSDPGSNNCHVTLMVTNGGDYGSPYGNIDFIEISARGLPSSLT
ADNVSRYLSIRRLGPTGLINSMQMRYGLVKDDGFIEVWAFQRAFINGAKVAVLAQTAR
TELYIPDGFVKQTAAPSGYVESPVVRIYDQLNKPTKADLGLSNAMLTGAFGLGGSGIST
NGKMSDVEILKALRDKGGHFWRGDKPTGSTATIYSHGSGIFSRCGDTWSAINIDYSTAKI
KIYAGNDARLNNGTFSINELYGSANKPSKSDVGLGNVTNDAQVKKTGDTMTGDLTIKK
GTPSVFLRADSGVTALRFYTGDNTERGIIYAGPNTDSLGEVRIRAKTAGGTSGGDLVVR
H
STF-62 (SEQ ID NO: 24)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAANSATAAKKSETNAKNSEAAAKVSETNAKASENKAKEYLDKVGGLVSPMTQY
DWPVVTASESLYIKIAKLSDPGTSRSHVTLMVTNAGNYGSPYGNIDFIEISARGLPSLLSA
DNVSRHLSIRRLGSTGLTDNNQMRYGLVKGDGFIEVWAFQGAFINDAKVAVLAQTTLN
TELYIPDGFVKQTAAPSGYIEGNVVRIYDQVNKPTKADLGLSNAMLTGAFGLGGSGIST
NGKMSDVEILKALRDKGGHFWRGDKPTGSTATIYSHGSGIFSRCGDTWSAINIDYSTAKI
KIYAGNDARLNNGTFSVNELYGSANKPSKSDVGLGNVTNDAQVKKSGDVMSGDLDIL
KETPSIRLKSAKGTAHLWFMNNDGSERGVVWSPENNESLGEIHIRAKNTKGESSGDFIV
RHDGRVEARNLKITYKISAATAEFANTSTSSDNTTVSIKGSQHTPLVLTSNNTIKNLSIGF
KVDDVDQKYLGIAGDGDLYFGSYSDHTKNSKVITQAKLDSGVTVGGKTTFSDLATFNA
GMAGSIEPETIDNKTIDLNDLIIANTVAGSVKYYQCKTVAGGAYITNKPDGVSGNFLLRV
ESTRKTTGSDYAIMQTLIGSDTKRIYVRFVVNGSWTEWSQVVVSGWNQDVTVRSLTSTT
PSKLGGGRVDVLGSTSDYSSMNCAVRGVDSTGTNSAWSVGTSKNTGKMLCLKNHRSS
AQVLLNGDDGAVQLLSGTVNGATAQALTINKDEVNSTADLVIRKQTGTGNRFALLNSG
NSELPVGIRVWGSSTRQNVFEVGTSTAYLFYAQKTSAGQLFDVNGAINCTTLNQSSDRD
LKDDILVISDATKAIRKMNGYTYTLRENGMPYAGVIAQEVMEAIPEAVGSFTHYGEELQ
GPTVDGNELREETRYLNVDYAAVTGLLVQFARETDDRVTALEEENTTLRQNLATADTRI
STLENQVSELVALVRQLTGSEH
STF-71 (SEQ ID NO: 25)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAASSATASANSQKAAKTSETNAKASETAAANSAKASAASQTAAKASEDAAREYA
SQAAEPYKQVLQPLPDVWIPFNDSLDMITGFSPSYKKIVIGDDEITMSGDKVVKFKRASK
ATYINKSGVLTEAAIDEPRFERDGLLIEGQRTNYMLNSESPASWGRSSNMDVPETGTDN
FGFTYGKFVCNDSLIGQTSAINMASIAATKSVDVSGDNKHVTTSCRFKTELQVRLRIRFD
KYDGSATTFLGDAYIDTQTLEINMTGGAASRITARVRKDEATGWIFAEATIQAIDGELKI
GSQIQYSPKQGGATVSGDYIYLATPQVENGPCVSSFIISGTTAATRASDIVTVPIKNNLYN
LPFTVLCEVUKNWYKTPNAAPRVFDTGGHQTGAAIILGFGSSADYDGFPYCDIGGANRR
VNENALLEKMVMGMRVKSDQSTCSVSNGRISSETKTTWSYIQNTAIIRIGGQTTAGLRH
LFGHVRNFRIWHKALTDAQVGESI
STF71-AP1 (SEQ ID NO: 26)
MKDLTLKLADRADFSAFMESTGYYDDESMQDDILIDVIGNVYKETGELNEDGEPVCVK
EDGYFVNVRIINDVKTPSIFDEYVVAVEHQLRGWM
3) INSERTION POINT MDETNR
STF-20 (SEQ ID NO: 27)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRRLAKNQNGADIQDK
SAFLDNIGVTSLTFMKNNGEMPVDADLNTFGPVKAYVGVWYKSTSSNATLEKNFPEDG
AVGVLEVFNGGNFSGMQRYTTRTGNVYMRNLSGTWNGSDGPWIYWRQIQSATRPLST
TIDLNTLGGAEHLGLWRNSSGSIASFDRNYPEEGSYGQGFLEVLEGGGYSRTQRYTTRR
GNVYVRCLSAIWNAQNPQWEPWSRVGHQSECRYYEGDLNDLTSPGIYSVTGKASNGP
MQDTAGATLLGILEVIRRFDGVSVWQRYTTTGKSETTQGRTFERVYAGSKWTEWREVY
NSFSLPLNLGIGGAVAKLSSLDWQTYDFVPGSLITVRLDNMTNIPDGMDWGVIDGNLINI
SVGPSDDSGSGRSMHVWRSTVSKANYRFFMVRISGNPGSRTITTRRVPIIDEAQTWGAK
QTFSAGLSGELSGNAATATKLKTARKINNVSFDGTSDINLTPKNIGAFASGKTGDTVAND
KAVGWNWSSGAYNATIGGASTLILHFNIGEGSCPAAQFRVNYKNGGIFYRSARDGYGFE
ADWSEFYTTTRKPTAGDVGALPLSGGQLNGALGIGTSSALGGNSIVLGDNDTGFKQNG
DGNLDVYANSVHVMRFVSGSVQSNKTINITGRVNPSDYGNFDSRYVRDVRLGTRVVQT
MQKGVMYEKAGHVITGLGIVGEVDGDDPAVFRPIQKYINGTWYNVAQV
STF20-AP1 (SEQ ID NO: 28)
MQHLKNITAGNPKTVAQYQLTKNFDVIWLWSEEGKNWYEEVSNFQEDTIKIVYDENNII
VGITRDASTLNPEGFSVVEVPDITANRRADDSGKWMFKDGAVIKRIYTADEQLQLAELQ
KSALLSEAETIIQPLERSVRLNIVIATDDERSRLEAWERYSVLVSRVDPANPEWPEMPQ
STF-23 (SEQ ID NO: 29)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLNSPALTGTPTT
PTARQGTNNTQIASTAFVMAAIAALVDSSPDALNTLNELAAALGNDPNFATTMTNALA
GKQPKDATLTALAGLATAADRFPYFTGNDVASLATLTKVGRDILAKSTVAAVIEYLGLR
ELGTSGEKIPLLSTANTWTNRQTFSGGLSGGLSGNAATATKLKTARKIAGVGFDGSSDISI
SAKNVNAFALRQTGNTVNGDTSVGWNWDSGAYNALIGGASALILHFNINAGSCPAVQF
RVNYKNGGISYRSARDGYGFELGWSDFYTTTRKPSAGDVGAYTRAECNSRFITGIRLGG
LSSVQTWNGPGWSDRSGYVVTGSVNGNRDELIDTTQARPIQYCINGTWYNAGSI
STF23-AP1 (SEQ ID NO: 30)
MMHLKNITAGNPKTKEQYQLTKQFNIKWLYSDDGKNWYEEQKNFQPDTLKMVYDHN
GVIICIEKDVSAINPEGASVVELPDITANRRADISGKWLFKDGVVIKRTYTEEEQRQQAEN
EKQSLLQLVRDKTQLWDSQLRLGIISDENKQKLTEWMLYAQKVESTDTSSLPVTFPEQP
E
STF-24 (SEQ ID NO: 31)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRRLQKDQNGADIPDK
RLFLRNIGATNSTTMSFSGGTGWFRLATVTMPQASSVVYISLIGGAGYNVNSPMQAGISE
LVLRAGNGNPKGLTGALWRRTSVGFTNFAWVNTSGDTYDVYVEIGNYATGVNIQWDY
TSNASVTIHTSPTYTANKPTGLTDGTVYVIYSSYIKPTAADVGALSLSGGQLNGALGIGTS
SALGGNSIVLGDNDTGFKQNGDGNLDVYANSVHVMRFVSGSVQSNKTINITGRVNPSD
YGNFDSRYVRDVRLGTRVVQTMQKGVMYEKAGHVITGLGIVGEVDGDDPAVFRPIQK
YINGTWYNVAQV
STF24-AP1 (SEQ ID NO: 32)
MQHLKNITAGNPKTVAQYQLTKNFDVIWLWSEEGKNWYEEVSNFQEDTIKIVYDENNII
VGITRDASTLNPEGFSVVEVPDITANRRADDSGKWMFKDGAVIKRIYTADEQLQLAELQ
KSALLSEAETIIQPLERSVRLNMATDEERSRLEAWERYSVLVSRVDPANPEWPEMPQ
O111-2.0 (SEQ ID NO: 33)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLNSPALTGTPTT
PTAPQGTNSTQIASTAFVMAAIAALVDSSPDALNTLSELAAALGNDPNFATTMTNALAG
KQPKDATLTALAGLVTAADRFPYFTGNDVASLATLTEVGRDILAKSTVAAVIEYLGLQE
TVNQASGALQKNQNGADIPGKDTFTKNIGACRAYSAWLNIGGDSQVWTTAQFISWLES
QGAFNHPYWMCKGSWAYANNKVITDTGCGNICLAGAVVEVIGTRGAMTIRVTTPSTSS
GGGITNAQFTYINHGDAYAPGWRRDYNTKNQQPAFALGQTGSRVANDKAVGWNWNS
GVYNADISGASTLILHFNMNAGSCPAVQFRVNYRNGGIFYRSARDGYGFEANWSEFYTT
TRKPSAGDVGAYTQAECNSRFITGIRLGGLSSVQTWNGPGWSDRSGYVVTGSVNGNRD
ELIDTTQARPIQYCINGTWYNAGSI
O111 2.0-AP1 (SEQ ID NO: 34)
MMHLKNITAGNPKTKEQYQLTKQFNIKWLYSEDGKNWYEEQKNFQPDTLKMVYDHN
GVIICIEKDVSAINPEGASVVELPDITANRRADISGKWMFKDGVVVKRTYTEEEQRQQAE
NEKQSLLQLVRDKTQLWDSQLRLGIISDENKQKLTEWMLFAQKVESTDTSSLPVTFPEQ
PE
STF-74 (SEQ ID NO: 35)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKYTAQDASTAQKGL
VKLSSATDSTSETLAATPKAVKAVNDNANGRVPSERKVNGHSLAGDISVTSQDIFDGQC
VEIGPGQDLDNYQTPGLYFQPANANTSAALHYPENNAGSLMVLRSAGITQVYRVYSGS
RSYLRSKYSTQPWTTWTPDDAFPVGAPIPWPSDTAPPAYALMQGQSFDKSAYPLLAVAY
PSGVIPDMRGQTIKGKPDGRAVLSYEQDGIKSHAHTASISDTDLGTKYTNSFDYGSKPTT
SFDYGNKSSTEGGWHVHNFRYCATSAYRDTPGSGLGMHSSNISWSAGDRIEGSGNHAH
VTWIGPHDHWVGIGEHNHYVVMGYHGHTATVHATGNTENTVKNIAFNYIVRLA
STF74-AP1 (SEQ ID NO: 36)
MAFEMTGENRTIILYNLRSDTNEFIGKSDGFIPANTGLPAYSTDIAPPKVTAGFVAVFDA
QTNKWSRVEDYRGTTVYDISTGKPAVIEKLGALPDNVVSVAPDGEYVKWDGAKWIHD
AEAEKTFRQGQAAQEKSNLLMIATSAIAPLQDAVDLDMATEDEATALNEWKKYRVML
NRVKPEDAPDITWPELPA
STF-86 (SEQ ID NO: 37)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRRVPASRKVNGHALN
GDINVTSRDIFDGQVIAIGANKNLDDYQVPGLYFQEANNNTSAAMNYPENSAGSLMVL
RGAGVTQVYRVYNSSRSYSRSKYSTLAWTPWMPEDSYPVGAPIPWPSDVTPTGYALMQ
GQPFDKAVYPLLAIAYPAGIIPDMRGQTIKGKPNGRAVLSYEQDGVISHTHGASISDTDL
GTKYTSSFDYGSKPTTSFDYGNKSSTEGGWHAHNFRYCATSAYRDTPGQGLGMHSSNV
SWAAGDRIEGSGNHAHVTWIGPHDHWVGIGAHNHYVVMGYHGHTATVHAAGNAENT
VKNIAFNYIVRLA
STF86-AP1 (SEQ ID NO: 38)
MTFEMTGENRTITIYNLRADTNEFIGKSDGFIPANTGLPANSTNIAPPPMKAGFVAVFNS
ASEKWSLVEDHRGKIVYDILTGKSITIDELGQLPDDVVSVAPEGHFVKWNGKKWVHDA
DAEKTAQITQATQQKDSLLALAASKIAPLQDAVDLDIATEEETALLLAWKKYRVLINRIK
PEDAPDIDWPEVPGDVA
STF-84 (SEQ ID NO: 39)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKYTAQDATTAQKGI
VQLSNATNSTSEMLAATPKSVKAAYDLANGKYTAQDATTAQKGIVQLSSATNSASETL
AATPKAANDNANGRVPSARKVNGKALSADITLTPKDIGTLNSTTMSFSGGAGWFKLAT
VTMPQASSVVSITLIGGAGFNVGSPQQAGISELVLRAGNGNPKGITGALWQRTSTGFTNF
AWVNTSGDTYDIYVAIGNYATGVNIQWDYTSNASVTIHTSPAYSANKPEGLTDGTVYSL
YTPSGQFYPPGAPIPWPSDTVPSGYALMQGQTFDKSAYPKLAAAYPSGVIPDMRGWTIK
GKPASGRAVLSQEQDGIKSHTHSASASSTDLGTKTTSSFDYGTKSTNNTGAHTHSVSGT
AASAGNHTHSVTGASAVSQWSQNGSVHKVVSAASVNTSAAGAHTHSVSGTAASAGAH
AHTVGIGAHTHSVAIGSHGHTITVNAAGNAENTVKNIAFNYIVRLA
STF84-AP1 (SEQ ID NO: 40)
MAFRMSEQPRTIKIYNLLAGTNEFIGEGDAYIPPHTGLPANSTYIAPPDIPAGFVAVFNSD
EGSWHLVEDHRGKTVYDVASGDALFISELGPLPENVTWLSPEGEFQKWNGTAWVKDA
EAEKLFRIREAEETKNSLMQVASEHIAPLQDAVDLEIATEEETSLLEAWKKYRVLLNRV
DTSTAPDIEWPTNPVRE
STF-93 (SEQ ID NO: 41)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRRVPSNRKVNGKALT
ADITLTPKDIGTLNSVTMSFSGGAGWFKLATVTMPQASSIVYIALIGGAGYNVGSPHQA
GISELVLRAGNGNPKGITGALWKRTAVGLTNFAWINTSGDTYDIYVEIGNYATSVNIEW
DCTANATVSIYTSPTYSASKPSSVTDGVVYTMYSTHQKPTPLDIGALPTTGGTVSGPLSV
TGGITGTLNGNASTATKLQTARSIGGVGFDGSANINLPGVNTTGNQNTTGNAATATKLQ
TARTIGGVSFDGTANINLPGVNTTGNQNTTGNAATATKLQTARTINGVSFDGSANISLSP
ANIGCPASPTGWLTTGSNGGAITTAQLVTLLQNNGAFNTKSWIARCAWAYANSATIPNS
ETGCGVIPLAGAVIEVFNNGSSSNNYTIRITTATTTSVSGALTNAEFIYVFNGTDYSPGWR
RVYNTKNKPTASDVGALPLTGGTLSGGLTSSGEIISKYANGFRIAYGSFGFFIRNDGSNTY
FMLTASGDTLGSWNGLRPITINNTSGAVSIGNGLNVTGGVNGSLNGNASTATKLQTARN
INGVKFDGSGDININTLVSRGRVTALSGSTQGTAGIQMYEAYNNSYPTTYGNVLHMKGA
SAAGEGELLIGWSGTSGAHAPVFIRSRRDTTDAAWSAWAQLYTAKDSIPGVNTTGNQN
TTGNAATATKLQTARKIAGVAFDGSADITLTAANLNAYTKTEVTNLLSSYASRSSLTGY
SGNLDIIAETLVVKSGGSGGFAIWDIGTTTSGANMYIDPNPGINTVWRSTSSRRYKKDIET
LQDRYADELLSLRPVWYRSICRGDRKDWGYYGLIAEEVGEIAPQYVHWREPTNNDSPE
DISSNGMVAEGVMYERLVVPLIHHIQQLTKRVEELETKLNSPKE
>STF-95 (SEQ ID NO: 42)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRRVPSARKVNGKALS
ADITLTPKDIGTLNSTTMSFSGGAGWFKLATVTMPQASSVVSITLIGGAGFNVGSPQQAG
ISELVLRAGNGNPKGITGALWQRTSTGFTNFAWVNTSGDTYDIYVAIGNYATGVNIQWD
YTSNASVTIHTSPAYSANKPEGLTDGTVYSLYTPSEQFYPPGAPIPWPSDTVPSGYALMQ
GQTFDKSAYPKLAAAYPSGVIPDMRGWTIKGKPASGRAVLSQEQDGIKSHTHSASASST
DLGTKNTSSFDYGTKSTNNTGAHTHSLSGSTGSAGDHTHGNGIRWPGGGGSALAFYDG
GGFTYVQDSQYQVSPGTSSRRSYYQRIQTQSAGAHTHSLSGTAASSGAHAHTVGIGAHT
HSVAIGSHGHTITVNAAGNAENTVKNIAFNYIVRLA
STF95-AP1 (SEQ ID NO: 43)
MAFRMSEQARTIKIYNLLAGTNEFIGEGDAYIPPHTGLPANSTDIAPPDIPAGFVAVFNSD
EASWHLVEDHRGKTVYDVASGDELFISELGPLPENVTWLSPEGEFQKWNGTAWVKDTE
AEKMFRIREAEETKNNLMQVASEHIAPLQDAADLEIATEEETSLLEAWKKYRVLLNRVD
TSTAPDIEWPTNPVRE
STF-132 (SEQ ID NO: 44)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRAVQRDGDTMTGEL
KIRGVNALRIFNDAFGLIFRRSEECLHLIPTSEGQGENGDIGPLRPFTINLRTGEISMSHKV
SVGGGSQVNGALGIGVQNALGGNSIAFGDNDTGIKQNGDGILDVYANGQHVFRFQNGA
LQSHRAVNVSGRVTPTDYGNFDERYQTKTGGVQNFQYTSEVFHKPAGNEVSWVFRAPS
GCTLSGINVQETGSNSADNIGGVYYKQAQIYINGAWRSVSG
STF132-AP1 (SEQ ID NO: 45)
MALSIRLIKAKIMELRNVTRYYPENMPYGEGVQYFRSEDGQDFYESLDKFAKKYKLCT
HPETGVIYSMAEDVSRLYPAGFTIVEVDELPDGFCIEARWYYKDGEVLPVPVDYRLLAE
SERARLTAIAEREISDKKTDLLLGIINNGEKEMLKLWRMYIRNLKNIDFNHIHDKSSFDSI
KWPCDPENSH
4) INSERTION POINT GAGENS
K1F (SEQ ID NO: 46)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSGAKGDGVTDDTAALTSALNDTPVGQKINGNGKTYKVTSLPDISRFINTRFVYERIPG
QPLYYASEEFVQGELFKITDTPYYNAWPQDKAFVYENVIYAPYMGSDRHGVSRLHVSW
VKSGDDGQTWSTPEWLTDLHPDYPTVNYHCMSMGVCRNRLFAMIETRTLAKNALTNC
ALWDRPMSRSLHLTGGITKAANQRYATIHVPDHGLFVGDFVNFSNSAVTGVSGDMTVA
TVIDKDNFTVLTPNQQTSDLNNAGKNWHMGTSFHKSPWRKTDLGLIPSVTEVHSFATID
NNGFAMGYHQGDVAPREVGLFYFPDAFNSPSNYVRRQIPSEYEPDASEPCIKYYDGVLY
LITRGTRGDRLGSSLHRSRDIGQTWESLRFPHNVHHTTLPFAKVGDDLIMFGSERAENE
WEAGAPDDRYKASYPRTFYARLNVNNWNADDIEWVNITDQIYQGGIVNSGVGVGSVV
VKDNYIYYMFGGEDHFNPWTYGDNSAKDPFKSDGHPSDLYCYKMKIGPDNRVSRDFR
YGAVPNRAVPVFFDTNGVRTVPAPMEFTGDLGLGHVTIRASTSSNIRSEVLMEGEYGFIG
KSIPTDNPAGQRIIFCGGEGTSSTTGAQITLYGANNTDSRRIVYNGDEHLFQSADVKPYN
DNVTALGGPSNRFTTAYLGSNPIVTSNGERKTEPVVFDDAFLDAWGDVHYIIVIYQWLDA
VQLKGNDARIHFGVIAQQIRDVFIAHGLMDENSTNCRYAVLCYDKYPRMTDTVFSHNEI
VEHTDEEGNVTTTEEPVYTEVVIHEEGEEWGVRPDGIFFAEAAYQRRKLERIEARLSALE
QK
K5 (SEQ ID NO: 47)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSPKTEGILHKGQSLYEYLDARVLTSKPFGAAGDATTDDTEVIAASLNSQKAVTISDGV
FSSSGINSNYCNLDGRGSGVLSHRSSTGNYLVFNNPRTGRLSNITVESNKATDTTQGQQV
SLAGGSDVTVSDVNFSNVKGTGFSLIAYPNDAPPDGLMIKGIRGSYSGYATNKAAGCVL
ADSSVNSLIDNVIAKNYPQFGAVELKGTASYNIVSNVIGADCQHVTYNGTEGPIAPSNNL
IKGVMANNPKYAAVVAGKGSTNLISDVLVDYSTSDARQAHGVTVEGSDNVINNVLMS
GCDGTNSLGQRQTATIARFIGTANNNYASVFPSYSATGVITFESGSTRNFVEVKHPGRRN
DLLSSASTIDGAATIDGTSNSNVVHAPALGQYIGSMSGRFEWRIKSMSLPSGVLTSADKY
RMLGDGAVSLAVGGGTSSQVRLFTSDGTSRTVSLTNGNVRLSTSSTGYLQLGADAMTP
DSTGTYALGSASRAWSGGFTQAAFTVTSDARCKTEPLTISDALLDAWSEVDFVQFQYLD
RVEEKGADSARWHFGIIAQRAKEAFERHGIDAHRYGFLCFDSWDDVYEEDANGSRKLIT
PAGSRYGIRYEEVLILEAALMRRTIKRMQEALAALPK
STF-37 (SEQ ID NO: 48)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSELSGEHGSFLIGGVIDCYSTVSDLISSSPSVGRVCRTIGYYSPGDGGGADYIISIGTPM
QDFSDSGSIVIDECKFAKLIQQSQYDLKQFGVKPSDPSYAEKNDIFISQAITRSRVGRCKIII
SDVIYHKKPLIFDYYNHMEGSCIGSDPEFTPRFIKIDNTTSGLPDMGYPGVADVVSYDVD
AGIIIKRQNSGTSFARGFIIKGFLLQSEKKSAWAIYAPHMADFDIDIDSRGFNGGIRWFVN
FLGRMAGRHIGLGANSSDPTLSIGAWCSKFSTIPDCGNSVVFRLSFNGFNRGMQMEYFG
NGVLDRVTLENISKPTPTSPTTHGIYATDTWLTGQVSCESSSTCIIRAGNNANFDITLSAV
FHVTQDDPSEGIVHVLNGGRLTLRSSTILADLADTKIINENGGYLDIAANTRTGNIVYSNS
DNYRFKDRTIGFGQTAATTKTSFSSGEEITFSLLNGTPKANLSGGTIQFNSPCLIKITVQGR
GITSGALTFGINGESSESVSQGQQVSMVVGVVSGDILNLKATSSLTLGSAGGVRVLLEPV
N
1JL (SEQ ID NO: 49)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSGYKVQSLAILSDTQAVHDATNTIKTQTDKIKADTQAIKTQTNQIKTETGVIRDKANT
AKTDAQAASAAAQGFRDQAKEWAQSVNADNLLTKTGNLAGLTDKSAARSNLGLGSV
ATENTVPIKKGGTAATTVAAARSNLGLGSVATENTVPIEKGGTAATTAAKARSNLGLGS
VATENTVPIEKGGTAATTAAKARSNFGLGDNNKVKLGTLRLNGGESLVFNDVERNGLII
SNASFGIDSWVGQTMHKWYTDWTRAGLVRAGDAHLSDYRVHVWKDGFTEALFRFLP
DGRLISGNSGNPSVNEFQKAPLSDRDLKKEIKYTDGEESYNRVRQWLPAMFKYKESDV
QRYGLIAQDLARIDPEYVHLLPGYAIYEDVKGVDEEGNEVVVDRKEIGYTDDVLSLDSN
VLLMDLCAAFVHLLHKVEKLEGK
STF-48 (SEQ ID NO: 50)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSQLESDADGMGDALVAVKQPYIGSIALTQHDKNTNFISAKDFGATADGTLHPLSEKF
STLSAAQAVYPFVTSLTQSLDYAGIQAAINTGRNVLLTSGTYFVNATIEMNSNCTINGET
NSNINRPETFIAVIGNIACFHYHAAFNTINIENVYIFYDGGRPTSPTGNDGKIGILIDGGTTS
PGVMHIKNVEVDGAWWAIYDDSGNYLTKYTQVWARRVAHGFYKANGTTIQWDTCYV
LDAAQAWYVVNCLSPQLINCAGDQITVDGSQYTFDSSGLYFSGCKCLTITGYDGESNIIK
NTNGITASYIKLNDTIAHISGLAGHGNSMQTTGSGTAAFIFATGTSIVNIKSSTDSFLDSESI
TYTGSGYPNTLLTDSTAKIIAEGCRFKAPTGGTPVISTYSTGNGVFTDCSLTGTQTSGSYV
ESRSSAGNQLPAVYTAKGTQAVAANVATTLFELPNSQGMYLISVWAESSGTNFSSLQLA
MWDGTTLTLTPLKSGGLISFTVTGRIVTITSQGTTTFNWTYTKAG
STF-49 (SEQ ID NO: 51)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSGAIGDGVHDDTSALSELLSVATGGEKIDGRGLTFKVSTLPDVSRFKNARFLFERIPG
QPLFYASEDFIQGELFKITDTPWYNAWTQDKTFVYDNVIYAPFMAGDRHGVNNLHVAW
VRSGDDGRTWTTPEWLTDLHENYPTVNYHCMSMGVVRNRLFAVIETRTVSGNKLQVA
ELWDRPMSRSLRAYGGITKAANQQVAYIRITDHGLFAGDFVNFSNSGVTGVTGNIVITVT
TVIDKNTFTVTTQNTQDVDQNNEGRYWSFGTSFHSSPWRKTSLGTIPSFVDGSTPVTEIH
SFATISDNSFAVGYHNGDIGPRELGILYFSDAFGSPGSFVRRRIPAEYEANASEPCVKYYD
GILYLTTRGTLSTQPGSSLHRSSDLGTSWNSLRFPNNVHESNLPFAKVGDELIIFGSERAF
GEWEGGEPDNRYAGNYPRTFMTRVNVNEWSLDNVEWVNVTDQIYQGGIVNSAVGVG
SVCIKDNWLYYIFGGEDFLNPWSIGDNNRKYPYVHDGHPADLYCFRVKIKQEEFVSRDF
VYGATPNRTLPTFMSTSGVRTVPVPVDFTDDVAVQSLTVHAGTSGQVRAEVKLEGNYA
IIAKKVPSDDVTAQRLIVSGGETTSSADGAMITLHGSGSSTPRRAVYNALEHLFENGDVK
PYLDNVNALGGPGNRFSTVYLGSNPVVTSDGTLKTEPVSPDEALLDAWGDVRYIAYKW
LNAVAIKGEEGARIHHGVIAQQLRDVLISHGLMEEESTTCRYAFLCYDDYPAVYDDVIT
GQREMPLTDNDGSIIVDEDDNPVMVMEDIIERVEITPAGSRWGVRPDLLFYIEAAWQRR
EIERIKARLDLIEGKH
STF-52 (SEQ ID NO: 52)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSQLASSEDGMGDALVAVKQPYIGSIALTQHDKNTNFISAKDFGATADGTLHPLSEKF
STLSAAQAVYPFVTSLTQSLDYAGIQAAINTGRNVLLTSGTYFVNATIEMNSNCTINGET
NSNINRPETFIAVIGNIACFHYHAAFNTINIENVYIFYDGGRPTSPTGNDGKIGILIDGGTTS
PGVMHIKNVEVDGAWWAIYDDSGNYLTKYTQVWARRVAHGFYKANGTTIQWDTCYV
LDAAQAWYVVNCLSPQLINCAGDQITVDGSQYTFDSSGLYFSGCKCLTITGYDGESNIIK
NTNGITASYIKLNDTIAHISGLAGHGNSMQTTGSGTAAFIFATGTSIVNIKSSTDSFLDSESI
TYTGSGYPNTLLTDSTAKIIAEGCRFKAPTGGTPVISTYSTGNGVFTDCSLTGTQTSGSYV
ESRSSAGNQLPAVYTAKGTQAVAANVATTLFELPNSQGMYLISVWAESSGTNFSSLQLA
MWDGTTLTLTPLKSGGLISFTVTGRIVTITSQGTTTFNWTYTKAG
1AR (SEQ ID NO: 53)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSIATRVSKEGDTMTGKLTLSAGNDALVLTAGEGASSHIRSDVGGTNNWYIGKGSGD
NGLGFYSYITQGGVYITNNGEIALSPQGQGTFNFNRDRLHINGTQWTAHQGGGWENQW
NQEAPIFIDFGNVGNDSYYPIIKGKSGITNEGYISGVDFGMRRITNTWAQGIIRVGNQENG
SDPQAIYEFHHNGVLYVPNIVIVKTGARLSAGGGDPVWQGACVVIGDNDTGLVHGGDGR
INMVANGMHIASWSSAYHLHEGLWDTTGALWTEQGRAIISFGHLVQQSDAYSTFVRDV
YVRSDIRVKKDLVKFENASEKLSKINGYTYMQKRGLDEEGNQKWEPNAGLIAQEVQAI
LPELVEGDPDGEALLRLNYNGVIGLNTAAINEHTAEIAELKSEIEELKKIVKSLLK
1AR-AP1 (SEQ ID NO: 54)
MAVTGPWVGSSAVVNTGQNWMVGAAQRLRMGAPFWMSNMIGRSVEVIHTLGADHN
FNGQWFRDRCFEAGSAPIVFNITGDLVSYSRDVPLFFMYGDTPNEYVQLNIHGVTMYGR
GGNGWAAGAIGASDGGVCIQNDIGGRLRINNGGAIAGGGGGGGGYSQANNWAGKYVC
GGGGGRPFGLGGNNGARWPGGNASLTSPGAGGNTGTRYYAGGGGEVGQPGQYANPG
AGYSTPPTSPGAAVAGSAPTWQNVGAIYGPRV
1AR-AP2 (SEQ ID NO: 55)
MSEQTIEQKLSAEIVTLKSRILDTQDQAARLMEESKILQGTLAEIARAVGITGDTIKVEEIV
EAVKNLTAESTDEAKDEE
13-13.0 (SEQ ID NO: 56)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGA
EAASAKATEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASE
AATSARDAVASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAER
SASAAADAKTAAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIAS
AVALEDADTTRKGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTA
PTALRGTNNTQIANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAG
KQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAG
ENSIIQLEDSQGAHFSTERTLATGAIKTRFFGETFTDGTLYLNQMNNSSERFSINNWGNSE
VGRPAVLEVGDSKGYHFYTERGTDNSLNFDVAGNFTVHGPSGITIKTSTGARHIWFRDD
SDAEKAVIWATDEGILHIRNNYGGSFSHHFQGAMILAGERVPYNSEYALIRGNISGGAW
VDWRGRPAGLLVDCQDSRNQAYNIWKATHWGDQHLAAMGVHAGGGNPQVVLHVGG
NDYAFASNGDFTAGAAVYCNDVYIRSDRRLKINVKDYEENAVDKVNKLKVKTYDKVK
SLSDREVIGHEIGIIAQDLQEVLPEAVSTSSVGSQDNPEEILTISNSAVNALLIKAIQEMSEE
IKELKTPLFTKIARKISKYFKF
13-13.0-AP1 (SEQ ID NO: 57)
MAVVGVPGWIGSSAVNETGQRWMSQAAGQLRLGVPCWMSQFAGRSREIIHTLGADHN
FNGQWFRDRCFEAGSTPIVFNITGDLVSYSKDVPLFFMYGDTPNEYVQLNIHGVTMYGR
GGNGGSNSPGSAGGHCIQNDIGGRLRINNGGAIAGGGGGGGGGRYGRLSFGGGGGRPF
GAGGSSSHMSSGATAGTISAPGAGSVGEGSLWVYTGGSGGNVGAAGGRCNIQGNGTEY
DGGAAGYAVIGSAPTWINVGAIYGPRV
13-13.0-AP2 (SEQ ID NO: 58)
MSEQTIEQKLSAEIVTLKSRILDTQDQAARLMEESKILQGTLAEIARAVGITGDTIKVEEIV
EAVKNLTAESADEAKDEE
5. INSERTION POINT SAGDAS
13-14.3 (SEQ ID NO: 59)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQ
YSVILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARN
ASVVAQSTADAKKSAGDASISDDIGWMHYIQRNKDNTVEAVLNGQQTINENIIAKKDIW
VDRAVHTLGEITTNAVNGLRIWNNDYGVIFRRSEGSLHIIPTAFGEGETGDIGPLRPLSIAL
DTGKVTIPDLQSSYNTFAANGYIKFVGHGAGAGGYDIQYAQAAPIFQEIDDDAVSKYYPI
VKQKFLNGKSVWSLGTEIESGTFVIREILKEDGSQGHASRFNQDGTVNFPDNVLVGGDIN
MKGMMTFDAGRLGSRDYFKFNHWGDSNNGRDNIIQLEDSQGAHFSTERTLATGAIKTR
FFGETFTDGTLYLNQMNNSSERFSINNWGNSEVGRPAVLEVGDSKGYHFYTERGTDNSL
NFDVAGNFTVHGPSGITIKTSTGARHIWFRDDSDAEKAVIWATDEGILHIRNNYGGSFSH
HFQGAMILAGERVPYNSEYALIRGNISGGAWVDWRGRPAGLLVDCQDSRNQAYNIWK
ATHWGDQHLAAMGVHAGGGNPQVVLHVGGNDYAFASNGDFTAGAAVYCNDVYIRS
DRRLKINVKDYEENAVDKVNKLKVKTYDKVKSLSDREVIGHEIGIIAQDLQEVLPEAVS
TSSVGSQDNPEEILTISNSAVNALLIKAIQEMSEEIKELKTPLFTKIARKISKYFKF
13-14.3-AP1 (SEQ ID NO: 60)
MAVVGVPGWIGSSAVNETGQRWMSQAAGQLRLGVPCWMSQFAGRSREIIHTLGADHN
ENGQWERDRCFEAGSTPIVFNITGDLVSYSKDVPLFFMYGDTPNEYVQLNIHGVTMYGR
GGNGGSNSPGSAGGHCIQNDIGGRLRINNGGAIAGGGGGGGGGRYGRLSFGGGGGRPF
GAGGSSSHMSSGATAGTISAPGAGSVGEGSLWVYTGGSGGNVGAAGGRCNIQGNGTEY
DGGAAGYAVIGSAPTWINVGAIYGPRV
13-14.3-AP2 (SEQ ID NO: 61)
MSEQTIEQKLSAEIVTLKSRILDTQDQAARLMEESKILQGTLAEIARAVGITGDTIKVEEIV
EAVKNLTAESADEAKDEE
Nucleotide Sequences
>STF-25 (SEQ ID NO: 62)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAgaaaca
gcagcggcatcgtccaggaacgcggcgaaaacatcagagacgaatgcaggtaacagcgcgaaagcggcagcttcttcaaaaacagcc
gcacaaaacgcagcaacagcggcagaacgttcagagacaaatgcccgtgcgtcagaagaagcctccgcagacagtgaagaggcttccc
gccgtaatgcagagtcagccgctgaaaatgccggagtcgccaccacaaaagcgcgggaggccgcagcagacgcaacaaaggccggg
cagaaaaaggatgaggctctgtcggcagcgacacgagctgaaaaggcggcagaccgcgcagaagccgcagcggaagtgactgcaga
gccctgtgcgaatatagtgccgccgctgcctgatgtgtggataccgtttaacgattcactggatatgattgcgggtttttctccgggctataaaa
aaatagctattggtgacgatgtggttcaggtcgccagtgataaacaggttaatttcagtcgcgcatcaacggcaacatatatcaacaaatctgg
cgaactgaaaacggcggaaattaatgagccgcgatttgagtgtgatggcctgatattgagggacaaagaacgaactacatgctcaattcgg
aaagtccagccagctgggggaagtcatcaaacatggatgtgcccgaaaccgggacggatagttttggttttacttatggaaagtttgtctgca
acgattctctggttgggcaaacttcggctattaatatggcatcaattgctgcaacaaagtcagttgatgtctcaggcgataacaagtacgtgac
aacctcatgccgttttaaaacagaacgacaggtaaggttacgtatacggtttgataagtatgatggtagtgcaacaacttttcttggcgatgcgt
acattgatacgcaaacgcttgaaattagtatgacaggtggtgctgccggcagaattacggcacgagtcaggaaggataagaccacgggct
ggatttttgcagaggcaacgattcaggcaattgatggtgagttaaaaataggctctcagatacagtattctcctgggcagggtggggcaaca
gtatctggtgactatatttatcttgccaccccacaagtagagaatgggccgtgtgtatcatcatttattatttcaggaggcagcgcaacgacaag
agccagtgatttggttagtatccccaccagaaataatctttataagttaccatttacttttttacttgagattcataaaaactgggatattgcaccaa
acgccgcaccccgcgtgtgggatatagcagcagccaataccgggcaatcagcaattgcagcaatcaacagaggtagtggtaagttatatat
gagtctgtcaaacccttcaggctcgtatgttaatagcgcagcgacagatgtatttgcagagaaaaccacatttggatgtattgcaaaagctgat
ggtcactttcatgtggtgacaaatggtaaagcggttaatgaagtttattgtgaatataatggcgtgaccgctgataaaaatatccgatttggagg
gcagacgaatactggagaacgacatctgtttggccatattcgcaatttccgcatatggcataaagaattaaatgacaggcaattaaaagaggt
cgta
STF-25-AP1 (SEQ ID NO: 63)
atgaaagatttaactttgaagtttcatgacaaactgcagtttaaggccttcctgtcatctcttggctgggcggaagatgaagacctccagaataa
actgttagttgatgaaattggtttcacctacacagaaacaggggtaacagaagagggagaacctgtctgtatccggaatgatggttattttgtc
aacattcgcattcttgatgacttgtttgatgtttctgtattctctgattatgtcgtggagctggaaacaccgcttcgggaatggagc
STF-27 (SEQ ID NO: 64)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAgaaacg
gcagcagcctcatcgaagaatgcggcgaaaacctcagaaacgaatgcagctaacagcgcacaggcggcagcggcctcgcagactgcat
cggcaaactccgcgacagcagccaaaaaatcagaaaccagcgcgaaaaatagcgagacagccacaaaggccagcgaaaaaaacgca
aaatccagccagacggcagcgaaaaccagtgagacgaatgccaaagacagtgaagccaacgcaaaggtgagcgaaacagcggcggc
gaactcggcgaaagcatcggcagcaagccagacggcagcaaaagcaagtgaagatgctgccagagaatacgcaaaccagacagcag
agccgtacagatatgttttacagccgctgccggatgtgtggataccctttaatgattcgctggatatgattacgggctattctccgggttataaaa
aagtgaagattggtgataatgtggttcaggttgccagtgataaacaggttaatttcagtcgcgcatcaacggcaacatatatcaacaaatctgg
cgaactgaaaacggcggaaattaatgagccgcgatttgagtgtgatggcctgatattgagggacaaagaacgaacttcttccagaacagta
cagacccttcgaagtggaataagtcaacttcactggacgttacagaaacaggcacagatagtttcgggtttaattatggtcggtttgtcgtaca
ggattcgattgttggtacaagtaaagcgcataccattatcggactgtattcgagtaccggaggggttgatacttcaggggacgaaaagcatgt
aactatatcctgtcgggtaaaaagtgaagttgataatatcgccgttcgtattttatttgaacattatgatggggaggtaaggacatcaataggag
cagcaaacctgaaccttaccacccgcataattagcaagacaggtcagacaagccgtgttacagcaaggtctgttaaggatgatgcaactgg
ctggatattttttgaggctacattaaaagcagatacaacagaaaatacggttggtggttttgtccagtattctccggatacagggcagatggtta
catcaggggattatctcgatgtaaccactccacagattgaggctggtacaggcgcatcatcttttattgttacggggacggcaccggcaacg
cgggcaagcgatatggtgacagtcccaatcaagaataacctttataatcttccttttacggttctttgtgaggtacataagaactggtataaaac
gccaaatgtagcgccgcgtgtttttgataccggcggtcatcaaaccggagcggggatcgtaatggggtttggttcatcaggtgggtacgac
ggttttccgtattgcgatataggtggttcagaccgacgaataaatgaaaatgccgggctggaaaaaatgcttattggtatgcgggtaaagtcc
gaacggtccacatgtgtagtcagtaacggtaagttaagcagcgaaactaaaaccaaatgggaatatatccggagtacagcaaccattcgca
ttggtggacaaactacagcaggattacgccatttatttgggcatgtgaggaattttcgtctctggcataaagagctaacagatgcgcagcttgg
ggaggttgtggag
STF27-AP1 (SEQ ID NO: 65)
gtgagagatttcacgttgcgtttcagtgataaagcagatttcagggcatttctcaggaaacttaactgggaagaggacgaagagctgcagaat
gccgttctggttgatgagattggttttacgttcagggagacagatgtttctgatgacggagaaccagaatacacgcgaaacgaagggtacttt
gttaatatccgtatcttgacgatggatttgaggattccgtgttccgtgagtgggtggttacaccagagcgcccgctcagggagtggttt
STF27-AP2 (SEQ ID NO: 66)
atgctgccgcagcatagcgatattgaaatagcctggtatgcttcgatacagcaggagccgaatggctggaagaccgtcaccacacagttct
acatccaggaattcagtgagtatattgcgccactgcaggatgctgtagatctggaaatcgcaacggaggaagaaagatcgttgctggaggc
atggaataaatatcgggtattgttgaatcgtgttgatacatcaactgcacctgatattgagtggccgacttcacctgcagag
STF-28 (SEQ ID NO: 67)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAgaaaca
gcagcggcatcgtccaggaacgcggcgaaaacatcagagacgaatgcaggtaacagcgcgaaagcggcagcttcttcaaaaacagcc
gcacaaaacgcagcaacagcggcagaacgttcagagacaaatgcccgtgcgtcagaagaagcctccgcagacagtgaagaggcttccc
gccgtaatgcagagtcagccgctgaaaatgccggagtcgccaccacaaaagcgcgggaggccgcagcagacgcaacaaaggccggg
cagaaaaaggatgaggctctgtcggcagcgacacgagctgaaaaggcggcagaccgcgcagaatccgcagcggaagtgactgcaga
gccctgtgcgaatatagtgccgccgctgcctgatgtgtggataccgtttaacgattcgctggatatgattacgggtttttcgccatcttataaaaa
gattgttattggtgacgatgaaataacaatgccaggcgacaagattgttaagtttaaacgtgcttcaacagcaacgtatattaataagtccggc
caactcaagcttgctgaagttgacgaaccgcgatttgagcgcgatggcttattgattgaaggacagaggacaaattatctgaggaactcaaat
aaaccagactcatggactgttcattccgcactgaataaaacatttggcactgataaacaggggttcaattatgccacggtgacacccacgga
aagtatagtgggaacaacaggtggctatactgtgcatggtgtggttgcagcagacagattcccgctggcaagtggtgaatgtttcactttttcg
tgccgggttaaaggcgctaaagcacgatgcaggttaagagtttcagttattattggtggaacagatacattctctgctgactcttatcttgatctg
gatacccggatcgcaacagtaagcggtaatacatcccttataacagccaaagctgaacaacagggcgagtggacctactatgaggccactt
atacagctaatacggacattgataccgttaactgtgctttttatatgacaaataaaataagtaatgagccattctatgatgactcaacattaaccat
gacgacgccgcaaattgaactgggcaatacggcatcgtcatttattgtaactacaatgccaacaacacgcgcaagtgatgtggttactatccc
ctcggcgaataacctgtcaacacggccttttacagtattgtgcgaagtaaggaggaactggagtacaccgcccaatgttgcgccaaggatat
ttgatgttggagggcacagtattgatgataattatttatcgctggggtttgtttcaacaggaaagataagcgccaacgtaggaatggttcagcc
acaaatttcctcagatggagaaaggttcattgtgggtgtgagagctaaatctgatttatcagtaaatgcaatatgcaatggtaattatacaacaa
accttaatggtaaaatatttggagttacagcaacatcgtaccggtttggtgggcagaccgcagcaggaacgcgtcatttgtttggacacatca
gaaatttcagagtctggtttaaagaattaaatgacaggcaaatcaaggaggcagta
STF28-AP1 (SEQ ID NO: 68)
atgaaagatttaactttgaaatttcctggtaacagagagtttaaatccttcctgtcatctcttgactgggaggaagatgaagacctccagaataa
actgttagtcgatgaaattggtttcacctacacagaaacaggggtaactgaagagggagaacctgtctgtatccggaataacggttattttgtc
aacattcgcattcttgatgacttgtttgatgtttctgtattctctgattatgtcgtggagctggaaacaccgcttcgggaatggagc
2) INSERTION POINT SASAAA
STF-15 (SEQ ID NO: 69)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAgcttctgcaactgcatc
agctaacagtcaaaaagcagcaaaaaccagtgaaaccaacgcaaaggtgagcgaaacagcggctgcgaactcagcgaaagcatcggc
agcaagccagacggcagctaaagcaagcgaagatgcagccagagagtatgcaagtcaggcagcagagccgtataaatatgtcttacagc
cactgcctgatgtgtggataccgtttaacgattcactggatatgattacgggcttttcgccgtcatataaaaaaattgttattggtgatgatgaaat
aacgatgcctggcgacaaggttgttaagtttaaacgcgcatcaactgccacatatatcaataaatcaggcgtatttagtgttgctaaaattgatg
agccacgatttgaaaaagaaggtttattgattgaaggacagcgcactaactattttgttaaatccaatactcccgctgaatggacgagtaccag
caatatcgataaaactaataatggtgttgatgaatttggtttttcatatgccaaaatgcgaacaaaagataatatgacaggacaatcatctgcact
tagtctgcatagatgcagtgcatcccgggggattgatgttagtggcgataataagtattgcactgtttcatgcagggttaaagctcctgatggtc
ttcgttgtcgtttgcgttttgaaaaatacgatgggtcggtttatacatttttaggagatgcttatttaactttcggaactctgataatagaaaaaactg
gcggggcagccaatagaatagcagctactgcaactaaagatccggttacagggtggattttctatgaggcaactatagaagctgttgaaggt
gaaaccttaattggcgcaatgattcagtatgcgccgaaaaaaggtggtataactgaagcgggagattatatttaccttgcaacaccacaatttg
aaaacggcggatgtgcttcatcttttgttattacgacaactgcacccgcaacccgctccagtgatatggtgacgattccaactaaaaataatatc
tataatagaccgcttacgtgtcttgtcgaggttaatagaatttggggcgatattcctcctaatgtagcaccgcgtatttttgatttttctggtgtgcc
acctattgagtcaattacatacgcttttaacacaactgagaaatattacggtcagattatatgcaaacttataaagcgtcgacaagtacttacgtt
tctagtgtgtttgctggtcgagctgatgttcgaaaattcattggtggttttaatatttattctgatggtactaaacgagtagtttctaacggtgaggct
actaaaactatgaaaacggagtggacgggcgtaaaaacacggacctttattcgaattggaggtcaagccacatcgggaactcgtcatctatt
cggccatttgagaaatcttcgtctctggcataaagaattaactgatgcgcaaatgggggagagtattaaa
STF15-AP1 (SEQ ID NO: 70)
atgaaagatttaacactcaaatttgcagacagggccgacttttcggcctttatggagagcattggctattatgatgacgagtcgatgcaggatg
atattcttattgacgtgataggtaatgtgtacaaagaaaccggagaacttactgaagatggcgagccggcatgtgttaaggaggacggatatt
ttgtaaatgtgcgcatcattaatgattcgcaaatatcgtcattattcgatgaacacgcggttgctgttgagcatcaactccgtagctggatg
STF15-AP2 (SEQ ID NO: 71)
atggctacatcgacagtaattcctgatgacatcaaaacgctaaagggagatgtcagtaaggcaaaggaagatatttcctcaattaacgtaaaa
gtatcaacgcttcagactgatatggacagtgcaaagcaggatatcagtaccagatacacaaaaacagaagtggataataagctgaaaaaca
aagtggaagtgaacgatctggaaagtggtcgttatggcggagatttttacccgctgactggccgtgaagcgttttatttatggggattgggca
caactacagcggcggcaaatctttatcttaatcctgaccctgcaatttcgtctgtgctgcggtcaacatcgtctatccgctataaacattcagtag
agacgatagattcagagcacgccgatctcattttcaggatgcgccctgtgtggtacaggtcgcaatgcgaaaatgacaggcgtgactgggg
attctatggattgattgccgaggaagtaggagaaattgcccctcagtttgttcactggcgaccagccaacgaagatgatgcaccggaaacca
tttccagcaatggccttgttgccgaaggtgtaatgtacgaacgtctggttgttccactgattcaccatatccagaaactgactgaaagagttgat
gaacttgagtcagaattgaagttgttatcaacttcccaaagcgatatcgga
STF-16 (SEQ ID NO: 72)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAgcttctgccactgcatc
agccaacagtcaaaaagcagcaaaaaccagtgaaaccaatgcaaagacaagcgagactgcagcggcgaactcggcgaaagcatccgc
tgcaagccagaccgctgcaaaagcaagtgaagacgcagccagagagtatgcaagccaggcagcagatccgtataaatatgtcttacagc
cgctgcctgatgtgtggataccgtttaacgattcactggatatgattacgggcttttcgccatcatataaaaagattgttattggtgacgacgaaa
taacgatgcctggcgacaagattgttaagtttaaacgtgcatcgaaagcaacctatattaacaaatctggtgtgctgacagaggctgccattga
tgagccacgatttgaacgtgatggcctgcttattgaggggcaaagaactaatcttctgcttaattcaacaaatccatctaaatggaataagtcag
gcaatctggaactcacagaaatatccacggattcttttaattttacttatgggagatttactgtaaaagatactcttattggtcagacaagtgctatt
aatatcgtaacgatttctggcagtaaagggtttgatgtcacaggtgatgaaaaatatgtgaccatttcatgccgtgtaagaagtgatgttgaaaa
tataaggtgtcgtttaagatttgaacaccatgatggttatacttacacttttttgggagatgcttacctcaatttatcaacacttgtaattgataaaact
ggtactgctgcagaccgtattattgcaaaggctgtaaaagatgaggttactggttggattttctatcaggctacaattaatgcactagatacaga
gagcatgattggtgcgatggttcaatacgctcctgtaaaaggttcaggtacagcatctggagactatctggatatcgcaactccacaagtgga
aggtggatcaagtgcttcgtcatttattgtaactgatataactgcaagcactcgcgcaagcgatatggtgacagtcccaatcaagaataaccttt
ataatcttccttttacggttctttgtgaggtacataagaactggtataaaacgccaaatgcagcaccgcgtgtttttgataccggcggtcatcaaa
ccggagcggctattattcttggcttcggtcgttcaacagattacgacggatttccttattgtgatataggtttggctaacagacgggtaaacgaa
aacgcatcgcttgaaaaaatggttatggggatgcgtgtaaagtcagatcagtctacgtgctcagtaagtaacgggcgtatatccagcgaaaa
gaaagccacatggtcctatattcagaactccgcaattatccgtattggaggccagactacagccgggttgcgtcatttatttggtcatgtcagg
aatttcagaatatggcacaaggcattgactgatgctcagatgggggagtcaatc
STF16-AP1 (SEQ ID NO: 73)
atgaaagatttaacactcaaatttgcagacagggccgacttttcggcctttatggatagcattggctattatgatgacgagtcgatgcaggatg
atattcttattgacgtgataggtaacgtgtacaaagaaaccggagaactgactgaagatggcgaaccggtatgtgttaaggaagatggatatt
atgtaaacgtgcgcatcattaatgatgcaaaaaaatcgtcaatattcgatgaatacgcggttgtagttgaacatcaacttcgtggctggatg
STF16-AP2 (SEQ ID NO: 74)
atggctacatcgacagtaattccaggagacatcaccacgttaaagggagatgtcagtaaagccaaggaagatatttcctcaattaacggaaa
agtatcaacgcttcaggctgatatgaccagtgcaaagcaggatatcagcaccagatacacaaaaactgaagttgataataagctgaaaaac
aaactggaagtgaacgctctggaaagcggtcgttatggtggagatttttacccgttgactggccgtgaagcgttttatttgtggggattgggca
cgactacagcggcggcaaacctttatcttaatcctgaccccgcaatttcgtctgtgctgcggtcaacatcgtctatccgctataaacattcagta
gagacaatagattcagagcacgccgatctcattttcaggatgcgccctgtgtggtacaggtcacaatgcgaaaatgacaggcgtgactggg
gattctacggattgattgccgaggaagtaggagaaattgcccctcagtttgtacactggcgaccagctaacgaagatgatgcaccggaagct
atttccagcaatggccttgttgccgaaggtgtaatgtacgaacgtctggttgttccactgattcaccatatccagaagctgactgaaagagttga
tgaacttgagtcagaattaaagttgttatccgtttcccgaagcgatatcgga
STF-17 (SEQ ID NO: 75)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAgcttctgccactgcatc
agccaacagtcaaaaagcagcaaaaaccagtgaaaccaatgcaaagacaagcgagactgcagcggcgaactcggcgaaagcatccgc
tgcaagccagaccgctgcaaaagcaagtgaagacgcagccagagagtatgcaagccaggcagcagatccgtataaatatgtcttacagc
cgctgcctgatgtgtggataccgtttaacgattcactggatatgattacgggcttttcgccatcatataaaaagattgttattggtgacgacgaaa
taacgatgcctggcgacaagattgttaagtttaaacgtgcatcgaaagcaacctatattaacaaatctggtgtgctgacagaggctgccattga
tgagccacgatttgaacgtgatggcctgcttattgaggggcaaagaactaatcttctgcttaattcaacaaatccatctaaatggaataagtcag
gcaatctggaactcacagaaatatccacggattcttttaattttacttatgggagatttactgtaaaagatactcttattggtcagacaagtgctatt
aatatcgtaacgatttctggcagtaaagggtttgatgtcacaggtgatgaaaaatatgtgaccatttcatgccgtgtaagaagtgatgttgaaaa
tataaggtgtcgtttaagatttgaacaccatgatggttatacttacacttttttgggagatgcttacctcaatttatcaacacttgtaattgataaaact
ggtactgctgcagaccgtattattgcaaaggctgtaaaagatgaggttactggttggattttctatcaggctacaattaatgcactagatacaga
gagcatgattggtgcgatggttcaatacgctcctgtaaaaggttcaggtacagcatctggagactatctggatatcgcaactccacaagtgga
aggtggatcaagtgcttcgtcatttattgtaactgatataactgcaagcactcgcgcaagcgatatggtgacagtcccaatcaagaataaccttt
ataatcttccttttacggttctttgtgaggtacataagaactggtataaaacgccaaatgcagcaccgcgtgtttttgataccggcggtcatcaaa
ccggagcggctattattcttggcttcggtcgttcaacagattacgacggatttccttattgtgatataggtttggctaacagacgggtaaacgaa
aacgcatcgcttgaaaaaatggttatggggatgcgtgtaaagtcagatcagtctacgtgctcagtaagtaacgggcgtatatccagcgaaaa
gaaagccacatggtcctatattcagaactccgcaattatccgtattggaggccagactacagccgggttgcgtcatttatttggtcatgtcagg
aatttcagaatatggcacaaggcattgactgatgctcagatgggggagtcaatc
>STF-17-AP1 (SEQ ID NO: 76)
atgaaagatttaacactcaaatttgcagacagggccgacttttcggcctttatggatagcattggctattatgatgacgagtcgatgcaggatg
atattatattgacgtgataggtaacgtgtacaaagaaaccggagaactgactgaagatggcgaaccggtatgtgttaaggaagatggatatt
atgtaaacgtgcgcatcattaatgatgcaaaaaaatcgtcaatattcgatgaatacgcggttgtagttgaacatcaacttcgtggctggatg
STF-13 (SEQ ID NO: 77)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAtcttctgccactgcatca
gccaacagtcaaaaagctgcaaaaaccagtgaaaccaacgcaaaggcgagcgagactgcggcggctaactcggcgaaagcatccgct
gcaagccagacggctgcaaaagcaagtgaagacgcagccagagagtatgcaagccaggctgcggagccgtataaacaagttttgcagc
cgcttcccgatgtgtggataccgtttaacgattcactggatatgcttgctggcttttcgcctggttataagcaaataactgtaggtgatgatgttat
taaaatgccatccgataaggttgttagcttcaaacgcgcatcaggtgcaacatacattaataaatcaggagtattaaccgttgctgaagttgac
gaaccgcgatttgaacgagaaggtttgctgattgaaggacaaagaaccaactatcatcttaattcacttacgccatctaagtggggagctaca
acaagtgtaactataacagaaagtggtgttgatgagtttggattacttatgggcggtttcaaataaaggacgaaaaaattgggacaaatacga
caatgaatatcgctgcggtttcaggaggaagaggtgtcgatgttactggaactgaaaagtatgttacaacatcatgtcgtgtaaaaagcgata
gtgctaatatacaatgtcgtataagatttgaaagatatgacgggtccgcatatttttatctggcagatgcatatcttaatataacagatatgtccatt
aggaaaacgggaggaggggctgcaagaataaccgcccgagcggagaaagaatctaatggatggatttatttcgaggttacatatcaatctg
aagctattgataatatggtGtggctctcagatccaaattgctccacctgtttcacctggaacttatttgggcggggaatatttggatgttacgaca
ccacaatttgaaggcggctcatgcgcatcatcttttatcatttccgatacagttgcatcaacgcgagcaagcgatattgttacattgccttgtaaa
aataacatggccagcaaacctttaacctgcatggttgaagtgaataaaaattggtctatagcaccaaattccgcgcctagaatttatgatataac
aggatttaaaacaaaagacgacgcttttgtttttgcattcagaaatacagcaggtagtgtaggaactccatatgttcaatttggtaatccaatatc
atttccacctggaaattacccaagaaagattatcgctgtatatagaataaaaagcgatggcaagtttcaggctggctgcaatggggttttatca
acaccagcatcaacaacgtggaagagtgttagtggtgctacaggtataaggattggaggccagactacagccggcttacgtcatttatttggt
tatatcaggaattttagaatatggcataaagaattaaccgatgcgcaaatgggagagataata
STF-13-AP1 (SEQ ID NO: 78)
atgcgagatttaattatcaaattcacagacaaggccgacttttcggcctttatgaagagtgctggctattatgatgacgagtcgatgcaggatg
atattcttattgacgtgataggtaacgtgtacaaagaaaccggagaacttactgaagatggcgagccggtatgtgttaaggaagacggatatt
ttgtaaacgtgcgcatcattaatgatgcaaaaaaatcgtcaatattcgataaatacgcggttgttgttgagcatcaacttcgtggctggatg
STF-13-AP2 (SEQ ID NO: 79)
atggctacatcgacagtaattccaggagatatcaccaagctaaagggggatgtcagtaaagctaaggaagatatttcatcaattagcagaaa
agtatcaacgcttcagactgagatgaccagtgcaaagcaggatatcagctccagatacacaaaaactgaagttgataataagctgaaaaac
aaagtggaagtgaacgatctggaaagtggtcgttatggcggagatttttatccactgacaggtcgtgaagcgttttatttatggaatttggccac
gactacagcggcggcaaacctttatcttaatcctgaccctgcaatttcgtctgtgctgcggtcaacatcgtctatccgctataaacattcagtag
agacaatagattcagagcacgccgatctcattttcaggatgcgccctgtgtggtacaggtcgcaatgcgaaaatgacaggcgtgactgggg
attctacggattgattgccgaggaagtaggagaaattgctcctcagtttgtacactggcgaccagctaacgaagatgatgctcctgaagctatt
tccagcaatggccttgttgccgaaggtgtaatgtacgaacgtctggttgttccactgattcaccatatccagaaactgactgaaagagttgatg
aacttgagtcagaattaaagttgttattaacttcccgaagcgatattaga
STF-12 (SEQ ID NO: 80)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAgcttctgccactgcatc
agcaaacagtcaaaaagctgcaaaaaccagtgaaaccaatgcaaagacaagcgagactgcagcggcgaactcggcgcaagcatcggc
agcaagccagacagcagctaaagcaagtgaggatgcagccagagagtatgcaagccaggcagcagagccgtataaatatgtcttacagc
cactgcctgatgtgtggataccgtttaacgattcactggatatgcttgctggcttttcgcctggttataagcaaataaccgtaggtgatgatgttat
taaaatgccatccgataaggttgttagcttcaaacgcgcatcaggtgcaacatacattaataaatcaggtgtattaaccgttgctgaagttgacg
aaccgcgatttgaacgagaaggtttgctgattgaaggacagagaacaaactatttcagaaattcaaatacaccagaagcatggaataacacg
ggtagtgtgtctgttgagtcgttcgacagtgataaggggtttaactatggaaggataactgttattaatgaaaatccgacagcacaaggatatc
aggcaattgctgtaaacacgaatgatgcttacacctgcccggcaggttcttatacgacgatatcgtgtctgacgaaaagtgataattcccggt
gtcgtgcaaggttcggaaaaatgtctgataatggtgcgtttgtttttcattcagatgcagttctggatcctgttacgggaaatgttgttcatggaaa
taatgtgacggtgacggcagaaagagtcggtgaatggtggttgtttaccgccactctttttgcagatgcggaaatgataatcagctcaagattt
gaaatcctggcgatgcctggaatcagtattatccccaatggctctacgttagatattgcgatgcctcaggcggagattgggtcgtacaggacg
tcatttatcattactgaaggggctcctggcactcgctccagcgacatggtgacaatacctgtaagaaacaatattcaccgattaccattcagtg
ctcttgttgaagttaataaaaactgggatatccctcccagcaaatcaccattaatctttaatgttaaagattatcaggaaaatggtctgttcacgca
tggattccgtggtaataatttctctgatgccggttctccttttatttctatgggagggtgtaataaatatgtggcaacaacccagaggaaaatcatt
tcaggcttccgttgtggcgctgatggagatgttcaggccgtatgtaatggtgaattatctgttgcggcaaaaacaacatggacttcaattgttcc
acgggcagtattgcgaattggagggcagggcactaatggggagtatcatctttttggtcatatccgtaatctgcgtatctggcataaagaatta
actgatgcgcaaatgggggagagtattaaa
STF-12-AP1 (SEQ ID NO: 81)
atgaaagatttaacactcaaatttgcagacagggccgacttttcggcctttatggagagtattggctattatgatgacgagtcgatgcaggatg
atattcttattgacgtgataggtaacgtgtacaaagaaaccggagaactgactgaagatggcgaaccggtatgtgttaaggaagacggatatt
ttgtaaacgtgcgcatcattaatgatgtaaaaaaatcgtcaatattcgataaatacgcggttgttgttgagcatcaacttcgtggctggatg
STF-12-AP2 (SEQ ID NO: 82)
atggctacatcgacagtaattccaggagatatcaccacgctaaagggagatgtcagtaaaactaaggaagatatttcctcaattaacggaaa
agtatcaacgcttcagactgatatgaccagtgcaaagcaggatatcagcaccagatacacaaaaactgaagttgataataagctgaaaaaca
aactggaagtgaacgatctggaaagcggtcgttatggtggagatttttacccgttgactggccgtgaagcgttttatatgtggggattgggca
cgactacagcggcggcaaacctttatcttaatcctgaccctgcaatttcgtctgtactgcggtcaacatcgtctattcgctataaacattcagtag
agacgatagattcagagcacgccgatctcattttcaggatgcgccctgtgtggtacaggtcgcaatgcgaaaatgacaggcgtgactgggg
attctacggattgattgccgaggaagtaggagaaattgcccctcagtttgtacactggcgaccagctaacgaagatgatgctcctgaagctat
ttccagcaatggccttgttgccgaaggtgtaatgtacgaacgtctggttgttccactgattcaccatatccagaagctgactgaaagagttgat
gaacttgagtcagaattaaagttgttatccgtttcccgaagcgatatcgga
STF-63 (SEQ ID NO: 83)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAAATTCCGCGA
CAGCAGCCAAAAAATCAGAAACCAACGCGAAAAATAGTGAGTCAGCAGCAAAGGT
CAGCGAAACCAACGCTAAAGCGTCAGAGAACAAGGCGAAAGAATATCTCGACAAG
GTCGGGGGACTCGTCAGCCCGATGACGCAATACGATTGGCCCGTTGTTACTGGTAAT
GAGTCTTTTTACATAAAGATCGCGAAACTTTCCGATCCCGGAAGCAACAATTGCCAT
GTAACGCTAATGGTTACTAACGGCGGTGACTACGGCTCCCCTTACGGAAACATTGAC
TTTATCGAGATCTCGGCGCGCGGTCTGCCTTCTTCGCTTACTGCTGATAATGTATCTC
GTTACCTGAGTATACGCCGTTTAGGGCCAACCGGGCTAATCAATAGCATGCAAATGC
GTTACGGCCTGGTTAAAGATGATGGCTTTATTGAGGTTTGGGCCTTCCAGCGTGCAT
TTATCAACGGCGCAAAGGTTGCGGTACTGGCGCAGACGGCACGCACGGAATTATAC
ATTCCAGACGGATTTGTTAAGCAAACCGCCGCGCCTTCTGGATATGTTGAAAGCCCC
GTTGTAAGGATTTACGACCAGTTAAACAAGCCGACTAAAGCAGATTTGGGTCTTTCT
AATGCTATGCTTACAGGCGCTTTCGGTCTTGGCGGTAGCGGGATATCAACAAACGGC
AAGATGAGCGATGTAGAGATCTTAAAAGCTCTGCGTGACAAAGGTGGTCATTTCTG
GCGCGGTGATAAGCCGACCGGAAGCACGGCGACCATTTATAGCCACGGTTCTGGTA
TATTCTCGCGGTGCGGCGATACGTGGTCAGCGATCAATATCGACTACTCAACCGCGA
AGATTAAGATCTATGCCGGCAACGATGCCCGGCTTAACAACGGGACTTTTAGCATCA
ATGAGCTATACGGCTCGGCAAACAAGCCGTCGAAATCGGATGTTGGACTTGGCAAC
GTAACGAACGATGCGCAGGTAAAAAAAACCGGCGATACAATGACCGGTGACTTGAC
AATCAAAAAAGGTACACCGTCAGTCTTCCTGCGGGCAGACAGTGGAGTCACCGCTTT
GCGGTTTTATACTGGCGATAACACAGAGCGCGGCATAATCTATGCTGGTCCTAACAC
TGATTCGCTTGGCGAAGTTCGCATCAGGGCAAAGACAGCAGGGGGGACATCAGGAG
GGGATCTTGTTGTTCGTCACGACGGGAGGGTTGAAGTCCGTGATCTCACAGTAGCGT
ATAAAATTAAAAGCAGAACGATTGAGATTGCAAATACCGATACTGACTCATCGGCA
ACTACGCTCAGCATCTATGGAGTACAGCACACGCCGTTGGTTTTAACGCGTTCTGGT
TCTTCTGAAAATGTGTCCATTGGGTTTAAGTTAGACAACATGAACCCAAAGTATCTT
GGAATTGATACTAATGGGGATCTGGCTTTTGGTGAGAGTCCTGATCAGAAACAAAA
CAGCAAATTGATCACGCAAGCGAAACTCGACAAGGGATTAACGATTGGTGGTCAAC
TGGCTTTCAAAGGTACGACAGCGTTTTCAGCCGTTGCTACGTTCATTGCCGGGATAG
CAGGAGCCATCGAGCCGGAAAACATTGACGGCCAGACGGTTAATCTTAACAACCTG
ACCATCATCAAGTCAGATGCCGGGGCAGTTAAATACTATATTTGTCCATCCTCTGCA
GGTGGTGCAAATATTACCAATAAGCCTGACGGCATAGCCGGTAACTTTTTGCTCCGT
GTAGAGTCGACTCGTAAGGTTAGGGATTCAGATTATGCGAACATGCAAACGCTGATT
AACAGCGACACAAAACGTATATACGTTCGCTTTGTTGTTAATGGAAACTGGACAGCG
TGGAGTCAGGTTGTTGTTTCCGGATGGAATCAGGATATAACTGTCAGGTCGTTAACC
ACATCTAGTCCGGTAAAATCTGGCGGAGGGCGAATTGATGTCCTTGGAAGCACGTC
AGACTATAGCAAAATGGATTGCTTTGTACGTGGGTTTGATAGCACCGGTAATTCTCT
CGCGTGGGCGTTGGGTTCATCAGCCGGCGTAAGTAAGATGCTGTCGCTAAAAAATTT
CTTTAGCGGAGCTGAGATACTGTTAAATGGTAATGACGGCACGGTTCAACTCAAAAC
AGGTGCTGTTAACGGGGCTACAGCGCAGGCGCTCACTATCAACAGGAATGAGGTTA
ACTCAACTGTTGATTTAACCCTTACAAAACAATCAGGGACTGGCAATCGTTTTGTTTT
ACAGAACTCAGGTAATGCAGAACTACCGTTTTCTGTCAGGGTGTGGGGTTCCAGTAC
TCGACAAAACGTTTTTGAGGTTGGCACGTCTGCTGCGTATCTGTTTTATGCGCAAAA
AACGTCAGCAGGCCAGTTGTTTGATGTAAATGGCGCTATTAATTGCACAACGCTGAA
TCAGTCATCAGACCGCGACCTTAAAGACGATATTCTCGTTATCAGCGACGCGACGAA
AGCAATCCGTAAAATGAACGGATACACCTACACGCTCAGGGAAAACGGGATGCCTT
ATGCTGGCGTTATTGCACAGGAAGTAATGGAGGCGATACCAGAAGCTGTGGGATCG
TTTACTCATTATGGTGAAGAGTTGCAAGGTCCGACCGTTGACGGCAACGAGCTACGC
GAAGAAACGCGCTATCTTAATGTTGACTACGCCGCCGTGACGGGCTTACTTGTTCAG
TTCGCCCGTGAAACAGATGATCGCGTTACCGCGCTGGAAGAGGAAAACACAACGCT
ACGTCAAAATCTGGCAACAGCAGACACCCGGATCAGCACTCTGGAAAATCAGGTAA
GCGAACTGGTTGCACTTGTCCGGCAGTTAACAGGAAGCGAACATTGA
STF-62 (SEQ ID NO: 84)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAAACTCCGCGA
CAGCAGCCAAAAAATCAGAAACCAACGCGAAAAATAGTGAGGCAGCAGCAAAGGT
CAGCGAAACCAACGCTAAAGCGTCAGAGAACAAGGCGAAAGAATATCTCGACAAG
GTCGGGGGACTCGTCAGCCCGATGACGCAATACGATTGGCCTGTTGTTACTGCTAGT
GAGTCTCTTTACATCAAGATCGCGAAACTTTCCGATCCTGGAACCAGCAGAAGTCAT
GTAACGCTAATGGTTACTAACGCTGGTAACTACGGCTCCCCTTACGGAAACATTGAC
TTTATCGAGATCTCGGCGCGCGGTCTGCCTTCTTTGCTTAGTGCGGATAATGTTTCTC
GTCATCTGAGTATACGCCGCTTAGGGTCAACCGGGCTGACCGATAACAACCAGATG
CGTTACGGCCTGGTTAAAGGTGACGGCTTTATTGAGGTTTGGGCATTCCAGGGTGCG
TTTATTAACGACGCAAAGGTTGCGGTGCTGGCGCAGACAACACTAAACACAGAATT
ATACATTCCAGACGGATTTGTTAAGCAAACCGCCGCGCCTTCTGGATATATTGAAGG
CAACGTTGTAAGGATTTACGACCAGGTAAACAAGCCGACTAAAGCAGATTTGGGTC
TTTCTAATGCTATGCTTACAGGCGCTTTCGGTCTTGGCGGTAGCGGGATATCAACAA
ACGGCAAGATGAGCGATGTAGAGATCTTAAAAGCTCTGCGTGACAAAGGTGGTCAT
TTCTGGCGCGGTGATAAGCCGACCGGAAGCACGGCGACCATTTATAGCCACGGTTCT
GGTATATTCTCGCGGTGCGGCGATACGTGGTCAGCGATCAATATCGACTACTCAACC
GCGAAGATTAAGATCTATGCCGGCAACGATGCCCGGCTTAACAACGGGACTTTTAG
CGTCAATGAGCTATACGGCTCGGCAAACAAGCCGTCGAAATCGGATGTTGGACTTG
GCAACGTAACGAACGATGCGCAGGTGAAAAAATCCGGCGATGTTATGTCTGGTGAT
CTTGATATATTGAAAGAAACGCCATCTATCAGGCTAAAATCAGCAAAAGGAACCGC
TCATCTGTGGTTCATGAACAACGACGGAAGCGAGCGCGGCGTTGTTTGGTCGCCTGA
AAACAACGAATCACTTGGCGAAATCCACATCAGGGCGAAAAACACAAAAGGTGAAT
CAAGTGGTGATTTTATTGTTCGCCACGACGGGAGGGTTGAGGCCCGCAATCTAAAAA
TAACTTACAAAATCAGCGCAGCCACCGCAGAATTTGCAAACACAAGCACCAGTTCC
GATAACACTACGGTAAGCATCAAAGGATCTCAGCATACGCCTTTGGTTTTAACGAGC
AACAACACAATTAAAAACTTGTCCATTGGGTTTAAGGTTGATGATGTTGATCAAAAA
TACCTAGGTATAGCTGGTGACGGTGATTTGTATTTTGGTAGTTATTCTGACCACACA
AAAAACAGCAAAGTAATCACACAAGCAAAACTCGATAGCGGGGTGACGGTAGGCG
GTAAAACAACCTTTTCTGACCTTGCCACATTTAACGCAGGTATGGCGGGATCTATCG
AGCCGGAAACCATTGACAACAAGACTATTGATTTAAACGACTTGATCATTGCTAATA
CAGTGGCTGGATCTGTTAAATACTATCAATGCAAAACTGTCGCAGGTGGTGCATATA
TTACCAATAAGCCTGACGGCGTAAGCGGTAACTTTTTGCTACGTGTAGAATCTACTC
GTAAAACTACGGGTTCAGATTATGCGATCATGCAAACGCTGATTGGCAGCGACACA
AAACGCATATACGTTCGCTTTGTTGTCAATGGAAGTTGGACGGAGTGGAGTCAGGTA
GTTGTTTCAGGATGGAATCAGGATGTAACCGTCAGGTCGTTAACCTCGACGACTCCA
TCAAAATTAGGCGGCGGGCGTGTTGATGTGCTGGGGAGTACGTCAGATTACAGTAG
TATGAATTGTGCTGTGCGCGGTGTTGATAGCACTGGAACCAATTCGGCGTGGTCAGT
AGGTACATCGAAAAACACGGGAAAAATGTTGTGCCTTAAAAACCACAGAAGCAGCG
CTCAAGTGCTGTTAAATGGCGATGATGGCGCGGTGCAACTACTAAGCGGTACTGTCA
ACGGTGCTACAGCACAGGCGCTAACCATCAACAAAGATGAGGTTAACTCAACTGCC
GATTTAGTAATTAGAAAACAAACAGGGACTGGCAATCGTTTTGCTTTACTTAATTCA
GGTAATTCAGAACTACCAGTTGGTATCAGGGTGTGGGGTTCCAGTACTCGTCAAAAC
GTTTTTGAGGTTGGAACGTCTACTGCGTATCTGTTTTATGCGCAAAAAACGTCAGCA
GGCCAGTTGTTTGATGTAAATGGCGCTATTAATTGCACAACGCTGAATCAGTCATCA
GACCGCGACCTTAAAGACGATATTCTCGTTATCAGCGACGCGACGAAAGCAATCCG
TAAAATGAACGGATACACCTACACGCTCAGGGAAAACGGGATGCCTTATGCTGGCG
TTATTGCACAGGAAGTAATGGAGGCGATACCAGAAGCTGTGGGATCGTTTACTCATT
ATGGTGAAGAGTTGCAAGGTCCGACCGTTGACGGCAACGAGCTACGCGAAGAAACG
CGCTATCTTAATGTTGACTACGCCGCCGTGACGGGCTTACTTGTTCAGTTCGCCCGTG
AAACAGATGATCGCGTTACCGCGCTGGAAGAGGAAAACACAACGCTACGTCAAAAT
CTGGCAACAGCAGACACCCGGATCAGCACTCTGGAAAATCAGGTAAGCGAACTGGT
TGCACTTGTCCGGCAGTTAACAGGAAGCGAACATTGA
STF-71 (SEQ ID NO: 85)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCATCTTCTGCCA
CTGCATCAGCCAACAGTCAAAAAGCTGCAAAAACCAGTGAAACCAACGCAAAGGC
GAGCGAGACTGCGGCGGCTAACTCGGCGAAAGCATCCGCTGCAAGCCAGACGGCAG
CTAAAGCAAGTGAAGATGCAGCCAGAGAGTACGCAAGCCAGGCTGCGGAGCCGTAT
AAACAAGTTTTGCAGCCGCTTCCCGATGTGTGGATACCGTTTAACGATTCACTGGAT
ATGATTACGGGCTTTTCGCCGTCATATAAAAAGATTGTTATTGGTGATGATGAAATA
ACGATGTCTGGCGATAAGGTTGTAAAGTTTAAACGCGCATCGAAAGCAACCTATATT
AATAAATCTGGTGTGCTGACAGAGGCTGCCATTGACGAGCCACGATTTGAACGTGAT
GGCCTGCTTATTGAGGGGCAAAGAACAAACTACATGCTCAATTCGGAAAGCCCTGC
CAGTTGGGGGCGATCGTCAAATATGGATGTGCCCGAAACAGGGACGGATAATTTTG
GTTTTACCTATGGAAAGTTTGTCTGCAACGATTCTCTGATTGGGCAAACCTCAGCCA
TTAATATGGCATCAATTGCTGCAACAAAGTCAGTTGATGTCTCAGGCGATAATAAAC
ACGTGACAACCTCATGTCGTTTTAAAACAGAACTGCAGGTAAGGTTGCGTATCCGGT
TTGATAAATATGACGGTAGCGCAACAACTTTTCTTGGTGATGCGTATATTGATACAC
AAACGCTTGAAATTAATATGACAGGCGGTGCTGCCTCAAGGATTACAGCGAGAGTC
AGAAAGGACGAAGCTACCGGATGGATTTTTGCAGAGGCAACAATTCAGGCAATTGA
TGGGGAGTTAAAAATAGGTTCTCAGATACAGTATTCTCCTAAGCAGGGCGGGGCAA
CCGTATCTGGTGACTATATTTATCTGGCCACCCCACAAGTAGAAAATGGGCCTTGTG
TATCATCTTTTATTATATCAGGAACGACGGCGGCGACCCGCGCAAGCGATATAGTCA
CAGTTCCCATTAAGAATAATCTTTATAATCTTCCTTTTACGGTTCTTTGTGAGGTACA
TAAGAACTGGTATAAAACGCCAAATGCAGCGCCGCGTGTTTTTGACACCGGCGGTC
ATCAAACCGGAGCGGCAATTATTCTTGGATTCGGTTCTTCAGCAGATTACGACGGAT
TTCCTTATTGCGATATTGGAGGAGCTAACAGACGGGTAAACGAAAACGCATTGCTTG
AAAAAATGGTTATGGGGATGCGTGTAAAGTCAGATCAGTCTACGTGCTCAGTAAGT
AACGGGCGTATATCCAGCGAAACAAAAACCACATGGTCCTATATTCAGAACACCGC
AATTATCCGTATTGGAGGCCAAACTACAGCCGGGTTACGTCATTTATTTGGTCATGT
CAGGAATTTCAGAATATGGCACAAGGCATTGACTGATGCTCAGGTGGGGGAGTCAA
TCTAA
STF-71-AP1 (SEQ ID NO: 86)
ATGAAAGATTTAACACTCAAATTAGCCGACAGGGCCGACTTTTCGGCCTTTATGGAG
AGTACTGGCTATTATGATGACGAGTCGATGCAGGATGATATTCTTATTGACGTGATA
GGTAACGTGTACAAAGAAACCGGAGAACTGAATGAAGATGGCGAACCGGTATGTGT
TAAGGAAGACGGATATTTTGTAAACGTGCGCATCATTAATGATGTGAAAACACCGTC
AATATTCGATGAATACGTGGTTGCTGTTGAGCATCAACTTCGTGGCTGGATGTGA
3) INSERTION POINT MDETNR
STF-20 (SEQ ID NO: 87)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTcgtctggcgaaaaatcagaacggtgcagatatccaggataaatcagcttttctggacaatattggtgttaccagcctgacgtttatgaa
aaacaacggcgaaatgccggttgatgctgatctcaatacatttggtccagttaaggcttatgtgggtgtctggtataaatccacatcctccaac
gcaacactggagaaaaatttccctgaagacggtgcagtcggtgttcttgaggtattcaatggcggtaatttttccggaatgcagcgttatacca
ccagaactggcaatgtttatatgcgtaatctttctggcacctggaatggctcagacggtccgtggatctactggcgtcagattcagtctgcaac
acgccccctgagcacaactattgacctgaacacgctaggaggcgcagagcatcttggtttatggcgaaacagtagtggctctatcgcttcatt
tgaccgcaactatccggaagaaggaagttatggtcagggattccttgaagttcttgagggtggtgggtactcacgcacgcaacgctatacga
cccgccgtgggaacgtatatgttcgctgcctttctgctatatggaatgcacagaacccacagtgggagccgtggtcaagagtaggccatca
gtcagaatgtcgttattacgaaggtgatttgaatgatctgacttcgccaggcatttacagcgttacagggaaggcgtcaaacggtccaatgca
ggataccgctggagcgacactgcttggaatactggaagtaatcaggcgttttgatggtgtatctgtctggcagcgttacacaaccacaggga
aatcagaaaccacacaggggcgcacttttgagcgcgtctatgccgggagcaaatggaccgaatggcgagaagtatataactccttttcgttg
cctctgaatctgggcatcggtggcgcagtggcaaaactatccagtctggactggcagacctacgattttgtgccgggcagtctgataaccgtt
cggcttgataatatgaccaacattcccgacggtatggactggggcgtcattgatggcaacctgataaacatctcagtcggtccgagtgatgat
tctggttcggggcgctcaatgcatgtatggcgcagcactgtaagtaaagccaactaccgcttttttatggtgcgcatttcaggaaatccggga
agccgcacgatcacaacaagacgagtaccaatcattgacgaagcccagacatggggcgcgaaacagacattcagtgctggcctttctggt
gaactgtccggcaatgcggcgacagcaacaaagctgaaaacagcccgtaaaattaataacgtttcgtttgatggaacatcagatattaacct
gacgccgaaaaatattggtgcatttgcttcaggaaaaacaggagacaccgttgcgaatgataaagccgttggatggaactggagtagcgga
gcctataacgcaactattggtggggcatcaacgttaattatcattttaatatcggggaaggaagttgtcccgccgcccagtttcgcgttaattat
aagaacggtggtattttttatcgttctgctcgtgacggttacggattcgaggctgactggtctgagttttataccacaacgcgaaaacctacagc
gggagatgtcggtgcactgccgttatctggtggtcaattgaatggtgctctgggtataggaacatccagtgctcttggcggtaattcgattgttt
tgggtgataatgacacgggctttaaacaaaatggtgatggtaatctggatgtttatgctaatagcgtccatgttatgcgctttgtctccggaagc
gttcaaagtaataaaaccataaatattacggggcgtgttaatccctcggattacggtaactttgattcccgctatgtgagagatgtcagacttgg
cacacgtgttgtccagaccatgcagaaaggggtgatgtatgagaaagcagggcacgtaattaccgggcttggtattgtcggtgaagtcgat
ggtgatgaccccgcagtattcagaccaatacaaaaatacatcaatggcacatggtataacgtcgcacaggtg
STF-20-AP1 (SEQ ID NO: 88)
atgcagcatttaaaaaatattactgcgggtaatccaaaaactgttgcccaatatcaactgacaaaaaattttgatgttatctggttatggtccgaa
gagggaaaaaactggtatgaggaagtaagtaattttcaggaagacacgataaagattgtttacgatgagaataatataattgtcggcatcacc
agagatgcttcaacgctcaaccctgaaggttttagcgttgtcgaggttcctgatattaccgccaaccgacgtgctgatgactcaggtaaatgg
atgtttaaggatggtgccgtgattaagcggatttatacggcagacgaacagctgcaactggcggaattacagaagtcagctttgctttccgaa
gctgaaactatcattcagccactggaacgctctgtcagactgaatatggcaacagatgatgagcgtagccgactggaagcatgggaacgct
acagtgttctggtcagccgtgtggatcctgcaaatcctgaatggccggaaatgccgcaa
STF-23 (SEQ ID NO: 89)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTaaagccccattaaacagcccggcgctgaccggaacgccaacaacaccaactgcgcgacagggaacgaataatacccaaatcgc
aagcacggctttcgttatggctgcgattgccgcccttgtagattcgtcacctgatgcactgaacacgctgaacgagctggctgcggcgttgg
gcaacgacccgaattttgcgaccaccatgactaacgcgcttgcgggtaagcaaccgaaagatgccaccctgacggcgctggccgggctt
gctactgcggcagacaggtttccgtattttacggggaatgatgtcgccagcctggcaaccctgacaaaagtcgggcgggatattcttgcgaa
atcgaccgttgctgccgttatcgaatacctcggtttacgagaactcggcacaagcggggagaaaataccgttactcagtacagcgaatacct
ggaccaatcgacaaacattcagcggtggcctttctgggggactgtccggcaatgccgctactgcaacaaagctgaaaacagcacgaaaaa
ttgctggagttggttttgatggttctagcgatatttcaattagtgccaaaaatgtcaatgcatttgcactccgacaaacaggtaatactgttaatgg
tgatacatccgttggatggaattgggatagtggtgcatataacgccctgattggtggtgcatctgcattaattcttcactttaatataaatgctggt
agctgtcctgccgtacaattccgtgtgaattataaaaatggtggcatttcctacaggtcggctcgtgatggttatgggtttgaattaggttggtca
gatttctataccacgacacgaaaaccttcagcgggagatgttggtgcatatacgcgggcagaatgtaactcaaggtttattacaggtattcgc
cttggcggtctgtcatctgttcagacatggaatggtcccggctggtctgacaggtcaggttatgtcgttacgggttcagttaacggaaaccgtg
atgaattaattgatacaacacaggcaaggccaattcagtattgcattaatgggacgtggtataacgcggggagtatttaa
STF-23-AP1 (SEQ ID NO: 90)
atgatgcacttaaaaaacattactgctggcaaccctaaaacaaaagagcaataccagctaacaaagcaatttaacatcaaatggctttattcag
atgatggaaaaaactggtatgaggaacaaaagaatttccagccagacactttgaaaatggtctatgaccataacggcgttattatttgtattgaa
aaggatgtttcagcaattaatccggaaggcgcaagcgtcgttgaattacctgatattacagcaaatcgccgggctgatatttcggggaaatgg
ttgttcaaagatggcgtagtgataaagcgaacttataccgaggaagagcagaggcaacaagcggaaaatgaaaagcaaagcctgttgcaa
cttgtcagggataaaacccagctatgggactcacagctacggctgggcatcatttccgacgagaataaacaaaaattaaccgagtggatgct
ctatgcgcagaaagtcgaatctacagacacctccagcctgccagtaacgtttcccgaacaaccagaa
STF-24 (SEQ ID NO: 91)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTcgtcttcagaaagatcagaacggtgcggatattcctgataaaagattattcctgcgcaatattggagcaacaaattcaacaaccatgtc
ttttagtggtggtacaggatggttcaggctggcaactgtaaccatgccccaggccagttccgtggtttacataagcctgattggtggtgccgg
atataatgttaactcccctatgcaggctggtatatctgaacttgttcttcgtgcgggaaatggaaatccaaaaggtcttactggtgcgttatggcg
acggacatcggttggatttactaattttgcatgggtgaatacatccggtgatacctatgatgtttatgttgaaataggtaattacgccacaggtgtt
aatattcagtgggattataccagtaacgccagcgtaacgattcatacatcaccaacttatacagcgaataaaccaacaggcctgacagatgg
aactgtatatgtaatttacagttcgtacattaaaccgactgctgctgatgttggggcgttatcattatctggtggtcaattgaatggtgctctgggt
ataggaacatccagtgctcttggcggtaattcgattgttttgggtgataatgacacgggctttaaacaaaatggtgatggtaatctggatgtttat
gctaatagcgtccatgttatgcgctttgtctccggaagcgttcaaagtaataaaaccataaatattacggggcgtgttaatccctcggattacgg
taactttgattcccgctatgtgagagatgtcagacttggcacacgtgttgtccagaccatgcagaaaggggtgatgtatgagaaagcagggc
acgtaattaccgggcttggtattgtcggtgaagtcgatggtgatgaccccgcagtattcagaccaatacaaaaatacatcaatggcacatggt
ataacgtcgcacaggtg
STF-24-AP1 (SEQ ID NO: 92)
atgcagcatttaaaaaatattactgcgggtaatccaaaaactgttgcccaatatcaactgacaaaaaattttgatgttatctggttatggtccgaa
gagggaaaaaactggtatgaggaagtaagtaattttcaggaagacacgataaagattgtttacgatgagaataatataattgtcggcatcacc
agagatgcttcaacgctcaaccctgaaggttttagcgttgtcgaggttcctgatattaccgccaaccgacgtgctgatgactcaggtaaatgg
atgtttaaggatggtgccgtgattaagcggatttatacggcagacgaacagctgcaactggcggaattacagaagtcagctttgctttccgaa
gctgaaactatcattcagccactggaacgctctgtcagactgaatatggcaacagatgaggagcgtagccgactggaagcatgggaacgc
tacagtgttctggtcagccgtgtggatcctgcaaatcctgaatggccggaaatgccgcaataa
O111-2.0 (SEQ ID NO: 93)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCTCCTCTGAACTCTCCGGCCCTGACTGGCACGCCTACTACTCCGACTGCG
CCGCAAGGGACCAACTCTACCCAGATTGCGTCCACGGCATTCGTTATGGCTGCTATT
GCAGCACTGGTAGATTCCTCGCCGGACGCTCTGAACACTCTGTCGGAACTGGCGGCT
GCACTCGGAAATGATCCGAACTTCGCCACCACCATGACTAACGCTCTGGCCGGCAA
ACAGCCGAAAGATGCTACCCTGACCGCCCTGGCAGGTCTCGTGACCGCTGCGGACC
GCTTCCCGTATTTCACAGGCAATGACGTTGCCTCCCTGGCTACCCTGACCGAGGTTG
GTCGTGACATCCTGGCGAAGTCTACCGTTGCGGCCGTGATTGAATATCTGGGTCTGC
AGGAAACTGTTAACCAGGCATCAGGTGCATTACAGAAGAATCAAAACGGTGCAGAC
ATTCCGGGCAAAGATACCTTTACCAAGAATATCGGTGCTTGTCGTGCTTATTCGGCA
TGGCTTAATATCGGAGGTGATTCTCAGGTATGGACTACGGCTCAGTTTATCTCTTGG
CTCGAGAGTCAGGGTGCGTTTAATCATCCGTACTGGATGTGCAAAGGCTCTTGGGCG
TACGCGAACAACAAAGTCATCACCGACACTGGTTGTGGTAACATCTGTCTGGCGGGT
GCAGTAGTGGAAGTTATCGGTACGCGCGGTGCGATGACGATCCGTGTAACTACTCCA
TCTACCTCCTCCGGTGGCGGTATCACCAACGCCCAGTTCACTTACATTAACCACGGC
GATGCCTATGCTCCGGGCTGGCGCCGTGATTACAACACTAAAAACCAACAACCTGC
GTTTGCACTGGGTCAGACGGGTAGTCGTGTGGCGAACGATAAAGCGGTCGGTTGGA
ATTGGAACTCTGGTGTGTACAACGCTGATATTAGTGGAGCTTCTACTCTGATCCTTCA
TTTTAACATGAATGCTGGAAGTTGTCCGGCAGTGCAGTTTCGTGTTAACTATCGTAA
TGGAGGAATCTTTTACCGCTCTGCACGTGACGGCTACGGCTTCGAAGCGAACTGGAG
TGAATTTTACACGACCACTCGTAAGCCGAGTGCTGGAGATGTGGGAGCTTATACTCA
GGCAGAATGCAATTCGCGTTTCATTACTGGTATTCGTCTGGGAGGTTTAAGTTCCGT
GCAGACTTGGAACGGTCCAGGTTGGAGTGATCGTAGTGGCTATGTTGTGACAGGCA
GTGTTAACGGCAACCGTGACGAACTGATCGACACTACTCAAGCGCGTCCGATCCAG
TACTGCATTAACGGAACTTGGTATAACGCGGGAAGTATCTAA
O111-2.0-AP1 (SEQ ID NO:  94)
atgatgcacttaaaaaacattactgctggcaaccctaaaacaaaagagcaataccagctaacgaaacaatttaacatcaaatggctttattcag
aggatggaaaaaactggtatgaggaacaaaagaatttccagccagacactttgaaaatggtttatgaccataacggcgttattatttgtattga
aaaggatgtttcagcaattaatccggaaggcgcaagcgtcgttgaattacctgatattacagcaaatcgccgtgctgacatttcgggtaaatg
gatgttcaaagatggcgtagtggtaaagcgtacttacacagaagaagagcaacgtcaacaggcggaaaatgaaaagcaaagcctgctaca
gctcgtcagggataaaacccagctatgggacagtcagctacggctgggcatcatttccgacgagaataaacaaaaattaacagagtggatg
ctattgcgcagaaagtcgaatctacagacacttccagcctgccagtaacgtttcccgaacaaccagaatga
STF-74 (SEQ ID NO: 95)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAATATACGGCTCAGGACGCGAGCACGGCGCAGAAAGGTCTGGTGAAACTGAG
CAGCGCCACCGACAGCACATCTGAGACCCTCGCCGCGACACCGAAAGCGGTTAAGG
CGGTGAATGATAATGCGAATGGTCGCGTCCCGTCTGAGCGAAAAGTTAACGGACAT
TCGCTGGCCGGTGATATCAGTGTCACCTCACAGGATATTTTTGACGGTCAGTGTGTT
GAAATTGGTCCGGGTCAGGATCTGGATAATTACCAGACGCCGGGTCTGTATTTTCAG
CCCGCAAATGCCAATACCAGTGCTGCTCTGCATTACCCGGAAAATAATGCCGGTTCC
CTGATGGTTTTAAGAAGCGCAGGGATAACGCAGGTTTATCGCGTGTACAGCGGTTCG
CGAAGTTATTTGCGGAGCAAATATTCCACGCAGCCATGGACGACGTGGACACCCGA
TGATGCTTTTCCTGTCGGCGCGCCGATTCCGTGGCCATCTGACATCGCCCCGCCCGCT
TACGCCTTAATGCAGGGGCAGTCATTTGATAAATCTGCATATCCATTGCTTGCTGTA
GCGTATCCCTCTGGTGTTATCCCGGATATGCGTGGTCAGACGATAAAGGGCAAGCCG
GACGGACGAGCGGTACTCTCGTATGAACAGGACGGTATTAAATCGCACGCTCATAC
AGCCAGTATTTCCGATACCGATTTGGGAACGAAATATACCAACTCTTTTGATTATGG
TTCAAAACCAACAACCAGTTTTGACTACGGCAATAAGTCCTCCACTGAGGGGGGAT
GGCACGTACATAACTTTCGTTATTGTGCTACGTCTGCATACCGGGATACTCCTGGCTC
AGGGCTGGGGATGCACTCGTCGAATATTTCGTGGTCAGCCGGGGATCGCATTGAGG
GGAGTGGTAATCATGCACATGTTACGTGGATTGGTCCCCATGATCACTGGGTTGGTA
TCGGTGAGCATAACCATTATGTGGTTATGGGGTATCACGGACATACAGCGACCGTTC
ATGCAACCGGGAATACAGAAAACACCGTTAAAAATATTGCGTTTAACTACATTGTG
AGGCTTGCATAA
STF-74-AP1 (SEQ ID NO: 96)
ATGGCTTTTGAAATGACCGGAGAAAACCGGACAATTATTCTTTATAACCTTCGTTCA
GATACAAATGAATTTATTGGGAAATCTGATGGGTTTATCCCTGCTAATACGGGCTTG
CCTGCTTACAGTACCGATATCGCGCCCCCAAAAGTGACGGCAGGTTTTGTGGCTGTT
TTCGATGCACAGACGAATAAATGGTCGCGGGTGGAGGACTACCGCGGGACAACCGT
CTATGACATCAGCACCGGTAAGCCCGCTGTTATTGAAAAACTTGGCGCTCTGCCTGA
TAACGTTGTGTCGGTTGCTCCTGACGGGGAGTATGTAAAATGGGATGGCGCTAAGTG
GATCCACGATGCCGAAGCGGAAAAAACATTTCGTCAGGGGCAGGCGGCGCAGGAA
AAATCAAACCTGCTGATGATTGCAACATCGGCTATTGCCCCCCTGCAGGATGCCGTT
GATCTGGATATGGCAACGGAAGACGAAGCGACCGCGCTTAATGAATGGAAAAAATA
CCGGGTCATGCTCAACAGAGTCAAACCCGAAGATGCCCCCGATATCACATGGCCGG
AACTGCCCGCATAA
STF86 (SEQ ID NO: 97)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTCGCGTTCCGGCATCACGAAAAGTGAACGGCCATGCCCTGAATGGAGATATCAA
TGTCACTTCACGGGATATTTTTGACGGCCAGGTTATAGCGATTGGTGCAAATAAGAA
TCTGGATGATTACCAGGTACCGGGGCTTTATTTTCAGGAAGCGAACAACAATACCAG
TGCAGCAATGAATTACCCGGAGAATAGCGCGGGTTCTCTGATGGTACTGAGAGGTG
CCGGAGTCACTCAGGTTTATCGTGTGTACAACAGCTCGCGCAGTTATTCGCGCAGCA
AGTATTCAACGCTGGCATGGACGCCGTGGATGCCAGAAGATTCTTACCCTGTCGGCG
CACCTATCCCCTGGCCATCGGATGTTACCCCGACAGGGTACGCCTTAATGCAGGGGC
AGCCCTTTGATAAAGCGGTCTATCCATTGCTAGCGATTGCCTATCCTGCGGGGATTA
TCCCGGACATGCGAGGCCAGACGATTAAGGGTAAACCGAACGGTCGCGCGGTACTC
TCGTATGAACAGGATGGTGTTATATCGCATACCCACGGAGCCAGTATTTCCGATACC
GATTTGGGGACGAAATACACCAGCTCTTTTGATTATGGTTCAAAACCAACAACCAGT
TTTGACTACGGCAATAAATCCTCCACTGAGGGTGGGTGGCACGCACATAACTTTCGT
TATTGCGCAACGTCTGCATACCGGGATACCCCCGGTCAGGGGCTGGGGATGCATTCG
TCTAATGTTTCATGGGCGGCGGGAGATCGCATTGAGGGAAGCGGTAATCATGCTCAT
GTGACATGGATCGGCCCTCATGATCACTGGGTGGGTATTGGTGCGCATAACCATTAT
GTGGTTATGGGCTATCACGGACATACAGCGACCGTTCATGCCGCAGGAAATGCGGA
AAATACCGTTAAAAATATTGCGTTTAACTACATTGTGAGGCTTGCCTGA
STF86-AP1 (SEQ ID NO: 98)
ATGACTTTTGAAATGACCGGAGAAAACCGGACAATTACCATCTATAACCTGCGTGCT
GATACAAATGAATTTATCGGGAAAAGTGATGGGTTTATCCCTGCTAATACCGGTTTG
CCTGCTAACAGTACCAATATTGCGCCACCGCCGATGAAAGCCGGTTTTGTCGCTGTA
TTTAATTCTGCGTCAGAAAAATGGTCACTTGTTGAAGACCATCGCGGGAAAATTGTT
TACGACATTCTCACCGGGAAATCCATCACGATTGATGAATTAGGTCAGTTACCTGAC
GACGTTGTTTCCGTTGCGCCGGAAGGCCATTTTGTTAAATGGAATGGTAAAAAATGG
GTGCATGATGCTGACGCAGAAAAAACGGCACAGATTACACAGGCTACACAGCAAAA
AGACAGTCTTCTGGCGCTGGCTGCATCAAAAATTGCCCCATTACAGGATGCTGTTGA
TCTGGATATTGCAACGGAAGAGGAAACAGCGCTTTTGCTGGCGTGGAAAAAATACA
GGGTTTTGATTAATCGTATTAAGCCAGAAGATGCGCCAGATATTGACTGGCCGGAGG
TTCCGGGCGATGTGGCGTGA
STF84 (SEQ ID NO: 99)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAATACACCGCACAGGATGCAACGACAGCACAGAAAGGGATAGTTCAGCTTAG
CAACGCGACCAACAGCACATCTGAAATGCTGGCGGCAACGCCAAAGTCGGTAAAGG
CAGCCTATGACCTTGCTAACGGGAAATATACTGCTCAGGACGCTACGACAGCACAA
AAAGGAATTGTCCAGCTCAGTAGTGCAACCAACAGCGCATCTGAAACGCTTGCCGC
GACACCGAAAGCAGCTAATGATAATGCGAATGGTCGGGTACCTTCTGCCCGTAAGG
TGAATGGTAAGGCGCTTTCAGCGGATATAACACTGACGCCGAAAGATATTGGTACG
CTTAACTCAACAACAATGTCATTCAGCGGTGGTGCTGGTTGGTTCAAATTAGCAACG
GTAACCATGCCACAGGCGAGTTCTGTTGTTTCAATTACGTTGATTGGTGGCGCGGGA
TTTAACGTGGGGTCACCTCAACAGGCAGGTATATCTGAACTTGTTTTGCGTGCAGGT
AATGGTAATCCGAAGGGGATTACTGGTGCTTTATGGCAGCGCACATCGACAGGGTTT
ACAAATTTTGCCTGGGTCAATACATCTGGTGATACTTACGATATTTACGTTGCAATC
GGAAATTATGCGACTGGTGTAAATATTCAATGGGATTATACCAGTAATGCCAGCGTG
ACGATTCATACGTCACCAGCATATTCTGCTAATAAGCCGGAAGGGTTAACGGACGGT
ACAGTTTATTCACTCTATACGCCATCAGGGCAGTTTTATCCGCCTGGCGCACCAATC
CCGTGGCCATCAGATACCGTTCCGTCTGGTTATGCCCTGATGCAGGGGCAGACTTTT
GACAAATCTGCTTACCCGAAACTCGCAGCCGCTTATCCGTCAGGCGTGATCCCTGAT
ATGCGTGGCTGGACGATTAAGGGCAAACCTGCCAGTGGTCGTGCCGTATTGTCTCAG
GAACAGGACGGCATTAAATCGCACACCCACAGCGCCAGCGCATCCAGTACGGATTT
GGGGACGAAAACCACATCGTCGTTTGATTACGGCACTAAATCCACGAATAACACCG
GGGCGCATACGCACAGTGTGAGCGGTACAGCCGCAAGTGCCGGAAACCATACTCAT
AGTGTCACAGGCGCATCAGCAGTCAGCCAGTGGTCACAAAATGGGTCAGTACATAA
GGTAGTGTCTGCGGCCAGTGTGAATACAAGTGCTGCAGGAGCGCACACTCATAGTG
TCAGCGGCACAGCCGCATCTGCAGGTGCTCACGCACATACTGTCGGTATTGGTGCTC
ATACGCACTCTGTTGCGATTGGCTCACATGGACACACCATCACCGTTAACGCTGCTG
GTAACGCGGAAAACACCGTCAAAAACATCGCATTTAACTACATTGTGAGGCTTGCAT
AA
STF84-AP1 (SEQ ID NO: 100)
ATGGCATTCAGAATGAGTGAACAACCACGGACCATAAAAATTTATAATCTGCTGGC
CGGAACTAATGAATTTATTGGTGAAGGTGACGCATATATTCCGCCTCATACAGGTCT
GCCAGCAAACAGTACCTATATTGCACCGCCAGATATTCCTGCTGGCTTTGTGGCCGT
TTTCAACAGTGATGAGGGATCGTGGCATCTCGTTGAAGACCATCGGGGAAAAACCG
TCTATGACGTGGCTTCCGGCGACGCGTTATTTATTTCTGAACTTGGCCCATTACCGGA
AAATGTCACCTGGTTATCCCCGGAAGGGGAGTTTCAGAAGTGGAACGGCACAGCCT
GGGTGAAAGATGCAGAAGCAGAAAAACTGTTCCGGATCCGGGAGGCGGAAGAAAC
AAAAAACAGCCTGATGCAGGTAGCCAGTGAGCATATTGCGCCACTTCAGGATGCTG
TAGATCTGGAAATCGCAACGGAGGAAGAAACCTCATTGCTGGAAGCCTGGAAAAAG
TATCGGGTGTTGCTGAACCGTGTTGATACATCAACTGCACCTGATATTGAGTGGCCT
ACGAACCCTGTCAGGGAGTAA
STF-93 (SEQ ID NO: 101)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAGGGTGCCATCTAACCGAAAAGTTAACGGTAAAGCACTGACTGCGGATATCAC
ATTAACGCCGAAAGATATTGGTACTTTAAATTCAGTAACGATGTCTTTCTCTGGCGG
GGCTGGGTGGTTCAAACTGGCTACGGTTACCATGCCACAAGCGAGTTCCATCGTTTA
CATCGCATTGATTGGTGGCGCTGGTTACAACGTCGGCTCCCCACATCAGGCAGGCAT
TTCAGAACTGGTTCTACGAGCAGGCAATGGAAACCCCAAAGGGATTACCGGTGCTTT
GTGGAAGCGTACAGCCGTCGGATTAACGAATTTCGCCTGGATCAACACATCCGGCG
ATACATATGATATTTACGTTGAGATTGGCAATTATGCGACTAGTGTAAATATCCATT
GGGATTGTACTGCAAATGCGACAGTTTCTATTTATACATCGCCAACATATTCAGCGA
GTAAGCCTTCCAGCGTTACCGATGGTGTTGTTTATACGATGTATAGCACACATCAGA
AACCGACGCCGTTAGATATTGGAGCACTGCCAACAACCGGAGGAACAGTTTCAGGT
CCGTTGTCTGTTACTGGTGGGATCACCGGAACATTAAATGGTAATGCAAGTACAGCA
ACGAAATTGCAGACGGCAAGATCTATCGGTGGAGTTGGTTTCGACGGTTCTGCAAAT
ATCAACCTTCCAGGTGTAAATACTACGGGTAATCAGAACACCACTGGTAATGCTGCA
ACTGCTACAAAACTTCAGACGGCAAGAACTATCGGCGGCGTGAGCTTTGATGGTACT
GCGAATATTAATTTGCCAGGTGTTAATACGACTGGTAATCAGAATACAACGGGCAA
CGCGGCTACTGCTACGAAGTTGCAGACTGCGCGTACTATCAATGGGGTGTCGTTTGA
CGGCTCGGCAAATATTTCCTTGTCGCCAGCAAATATAGGTTGCCCGGCATCTCCTAC
TGGTTGGTTAACTACAGGAAGTAATGGCGGAGCAATAACAACAGCACAGTTAGTGA
CGTTATTGCAAAATAATGGAGCATTTAACACAAAGTCATGGATTGCTCGATGTGCGT
GGGCCTATGCCAATAGTGCAACCATACCAAATAGTGAAACTGGTTGTGGCGTTATTC
CATTGGCAGGAGCTGTTATAGAGGTATTTAATAACGGTAGTAGCTCAAACAATTATA
CGATCCGTATAACAACGGCCACAACGACGAGTGTCTCTGGTGCTCTCACTAATGCGG
AGTTTATCTATGTATTTAATGGCACAGATTATTCTCCGGGATGGCGAAGAGTATATA
ACACGAAAAACAAACCAACAGCCTCTGATGTCGGTGCATTACCTCTTACCGGTGGTA
CATTATCTGGAGGTTTGACATCTTCTGGCGAGATCATTTCAAAATATGCAAATGGTT
TCCGCATTGCTTACGGTAGCTTTGGGTTCTTTATCCGTAATGATGGATCGAACACATA
TTTCATGCTAACAGCATCAGGAGACACATTAGGTTCATGGAACGGTTTGCGACCTAT
TACAATTAATAATACCAGCGGTGCGGTATCAATTGGTAATGGACTAAATGTGACTGG
TGGCGTAAATGGTAGTTTGAACGGTAATGCTTCAACAGCTACGAAGTTGCAAACAG
CGAGAAACATCAATGGTGTTAAGTTTGATGGCTCAGGCGATATCAACATTAATACAC
TGGTATCTCGTGGCCGAGTTACGGCATTAAGCGGCTCTACTCAAGGCACTGCTGGCA
TTCAAATGTACGAGGCGTACAACAATAGCTACCCGACCACGTATGGCAACGTATTGC
ACATGAAAGGTGCGAGTGCTGCTGGTGAGGGCGAGTTGCTTATTGGCTGGAGTGGT
ACGAGCGGTGCACATGCGCCAGTTTTCATTCGCTCACGAAGAGATACCACAGATGC
GGCATGGTCAGCGTGGGCGCAGCTATATACTGCTAAGGATTCAATCCCTGGTGTGAA
TACAACCGGTAATCAGAATACTACTGGTAATGCCGCAACAGCCACAAAATTGCAGA
CAGCAAGGAAAATTGCTGGTGTGGCGTTTGATGGCTCTGCCGATATTACTTTGACTG
CGGCTAACCTTAATGCTTATACGAAAACAGAGGTAACAAACCTTCTAAGTTCCTATG
CAAGCAGATCATCACTGACAGGCTATAGTGGCAACCTGGATATTATTGCTGAAACAC
TGGTTGTCAAATCAGGCGGTAGTGGAGGGTTTGCTATATGGGATATTGGCACAACTA
CTAGCGGTGCCAATATGTACATTGATCCAAACCCTGGTATCAATACAGTTTGGCGTT
CAACATCTTCAAGGCGCTATAAAAAGGATATTGAAACATTACAAGATCGATATGCT
GATGAACTTTTGTCATTAAGACCTGTTTGGTATCGTTCAATTTGTCGAGGTGACCGA
AAGGATTGGGGGTATTACGGCCTTATTGCTGAAGAGGTTGGTGAGATTGCCCCGCAA
TATGTCCATTGGCGTGAACCAACAAATAATGATTCTCCAGAAGATATTTCCTCAAAT
GGTATGGTCGCTGAAGGGGTGATGTATGAGCGTTTGGTTGTACCACTCATTCATCAT
ATTCAGCAATTGACCAAAAGGGTTGAGGAGCTTGAAACGAAGTTAAATTCACCTAA
AGAA
STF-95 (SEQ ID NO: 102)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTCGGGTACCTTCTGCCCGTAAGGTGAATGGTAAGGCGCTTTCAGCGGATATAACA
CTGACGCCGAAAGATATTGGTACGCTTAACTCAACAACAATGTCATTCAGCGGTGGT
GCTGGTTGGTTCAAATTAGCAACGGTAACCATGCCACAGGCGAGTTCTGTTGTTTCA
ATTACGTTGATTGGTGGTGCGGGATTTAACGTGGGGTCACCTCAACAGGCAGGTATA
TCTGAACTTGTTTTGCGTGCAGGTAATGGTAATCCGAAGGGGATTACTGGTGCTTTA
TGGCAGCGCACATCGACAGGGTTTACAAATTTTGCCTGGGTCAATACATCTGGTGAT
ACTTACGATATTTACGTTGCAATCGGAAATTATGCGACTGGTGTAAATATTCAATGG
GATTATACCAGTAATGCCAGCGTGACGATTCATACGTCACCAGCATATTCTGCTAAT
AAGCCGGAAGGGTTAACGGACGGTACAGTTTATTCACTCTATACGCCATCAGAGCA
GTTTTATCCGCCTGGCGCACCAATCCCGTGGCCATCAGATACCGTTCCGTCTGGCTA
TGCCCTGATGCAGGGGCAGACTTTTGACAAATCTGCATACCCGAAACTTGCAGCCGC
TTATCCGTCAGGCGTGATCCCTGATATGCGTGGCTGGACGATTAAGGGCAAACCCGC
CAGTGGTCGTGCCGTATTGTCTCAGGAACAGGACGGCATTAAATCGCACACCCACA
GCGCCAGCGCATCCAGTACGGATTTGGGGACGAAAAACACATCGTCGTTTGATTAC
GGAACCAAATCCACGAATAACACCGGGGCGCATACGCACAGTCTGAGTGGCTCTAC
GGGGTCTGCCGGTGATCATACTCATGGTAATGGTATTCGTTGGCCAGGAGGCGGCGG
TTCTGCGTTAGCATTTTATGATGGCGGTGGGTTCACTTATGTCCAGGATTCACAGTAT
CAAGTAAGCCCGGGGACTTCTTCCCGTAGATCGTATTATCAACGTATTCAGACACAG
TCAGCAGGTGCTCATACCCACTCGCTGTCTGGTACTGCAGCAAGTTCTGGCGCACAT
GCACATACTGTAGGTATTGGTGCGCATACGCACTCCGTTGCGATTGGTTCACATGGA
CACACCATCACCGTTAACGCTGCTGGTAACGCGGAAAACACCGTCAAAAACATCGC
ATTTAACTATATTGTGAGGCTTGCATAA
STF-95-AP1 (SEQ ID NO: 103)
ATGGCATTCAGAATGAGTGAACAAGCACGGACCATAAAAATTTATAATCTGCTGGC
CGGAACTAATGAATTTATTGGTGAAGGTGACGCATATATTCCGCCTCATACAGGTCT
GCCAGCAAACAGTACCGATATTGCACCACCAGATATTCCTGCTGGCTTTGTGGCTGT
TTTCAACAGTGATGAGGCATCGTGGCATCTCGTTGAAGACCATCGGGGTAAAACGGT
TTATGACGTAGCGTCAGGGGACGAGTTATTTATTTCTGAACTCGGTCCGTTACCGGA
AAATGTTACCTGGTTATCGCCGGAAGGGGAGTTTCAGAAGTGGAACGGCACAGCCT
GGGTGAAGGATACGGAAGCAGAAAAAATGTTCCGGATCCGGGAGGCGGAAGAAAC
AAAAAACAACCTGATGCAGGTAGCCAGTGAGCATATTGCGCCGCTTCAGGATGCTG
CAGATCTGGAAATTGCAACGGAGGAAGAAACCTCATTGCTGGAAGCCTGGAAAAAG
TATCGGGTGTTGCTGAACCGTGTTGATACATCAACTGCACCTGATATTGAGTGGCCT
ACGAACCCTGTCAGGGAGTAA
STF-132 (SEQ ID NO: 104)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTGCCGTTCAGCGTGATGGTGACACCATGACCGGGGAACTGAAAATCCGTGGTGTT
AATGCGCTGAGGATTTTCAACGACGCCTTTGGTCTGATTTTTCGTCGTTCAGAAGAG
TGCCTGCACCTTATCCCTACCAGTGAAGGTCAGGGCGAGAATGGCGATATTGGTCCA
CTTCGCCCGTTCACTATTAATCTGCGGACGGGTGAAATATCCATGTCGCATAAAGTG
TCTGTTGGCGGCGGTTCTCAGGTCAATGGTGCGCTGGGTATCGGCGTTCAGAACGCG
CTGGGCGGAAACTCAATTGCTTTCGGGGATAACGATACAGGTATAAAACAAAACGG
CGACGGCATTCTGGATGTTTATGCGAATGGACAGCACGTATTCCGTTTTCAGAATGG
CGCGTTACAAAGTCACCGGGCAGTGAATGTTTCAGGGCGGGTAACACCAACTGATT
ATGGCAATTTCGATGAACGCTACCAGACCAAAACAGGCGGCGTGCAGAATTTTCAG
TACACCAGTGAGGTGTTTCACAAGCCAGCCGGTAATGAGGTTTCCTGGGTTTTTCGG
GCGCCGTCAGGTTGCACTCTTTCTGGGATTAATGTGCAGGAGACCGGTAGTAACTCT
GCGGATAATATCGGTGGTGTGTATTACAAACAGGCCCAGATTTATATAAATGGCGCA
TGGCGCTCAGTATCAGGTTAA
STF-132-AP1 (SEQ ID NO: 105)
ATGGCGCTCAGTATCAGGTTAATTAAGGCAAAAATAATGGAACTCAGAAATGTCAC
GCGTTATTACCCGGAAAACATGCCTTATGGTGAAGGTGTTCAGTATTTCCGTAGTGA
AGACGGGCAGGATTTTTATGAATCACTGGATAAATTCGCGAAGAAATACAAGCTGT
GCACGCATCCTGAAACCGGTGTTATTTATTCAATGGCGGAAGACGTATCCCGGCTTT
ATCCGGCAGGTTTCACCATTGTGGAAGTGGATGAACTACCGGATGGCTTTTGTATAG
AGGCGCGCTGGTATTATAAAGACGGTGAAGTACTGCCGGTTCCTGTTGATTACAGAC
TGCTGGCTGAGTCGGAACGAGCACGTCTTACGGCGATTGCTGAACGGGAAATATCC
GACAAGAAAACAGATTTACTTCTGGGAATAATTAATAATGGGGAAAAAGAAATGCT
GAAATTATGGCGGATGTACATCAGAAATTTAAAGAATATTGATTTTAATCACATTCA
TGATAAATCGTCATTTGATAGTATTAAATGGCCTTGTGATCCTGAGAATTCACATTA
A
4) INSERTION POINT GAGENS
K1F (SEQ ID NO: 106)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATCTGGACAGT
CCGGCACTGACCGGAACGCCAACAGCACCAACCGCGCTCAGGGGAACAAACAATAC
CCAGATTGCGAACACCGCTTTTGTACTGGCCGCGATTGCAGATGTTATCGACGCGTC
ACCTGACGCACTGAATACGCTGAATGAACTGGCCGCAGCGCTCGGGAATGATCCAG
ATTTTGCTACCACCATGACTAACGCGCTTGCGGGTAAACAACCGAAGAATGCGACA
CTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAATAAATTACCGTATTTTGCGGAA
AATGATGCCGCCAGCCTGACTGAACTGACTCAGGTTGGCAGGGATATTCTGGCAAA
AAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCCGGTGAGAATTCGGGTGCGAA
GGGCGATGGCGTTACCGACGACACTGCAGCGCTGACTTCCGCCCTGAACGATACTCC
GGTGGGTCAGAAAATCAACGGTAACGGTAAAACTTATAAAGTTACGTCCCTGCCGG
ACATCTCCCGCTTTATCAACACCCGTTTCGTGTATGAACGTATCCCAGGCCAGCCGC
TGTACTACGCATCGGAAGAGTTCGTTCAGGGTGAGCTTTTTAAAATCACCGACACTC
CGTATTATAACGCCTGGCCACAGGATAAGGCTTTCGTGTACGAAAACGTTATCTATG
CTCCGTACATGGGTTCCGACCGTCACGGTGTCAGCCGACTGCACGTAAGCTGGGTGA
AATCGGGCGACGATGGTCAGACCTGGAGCACGCCTGAGTGGCTGACCGACCTTCAT
CCGGACTATCCGACCGTTAACTATCACTGCATGAGCATGGGCGTCTGTCGCAACCGT
CTGTTCGCAATGATCGAAACCCGTACGCTGGCAAAAAACGCTCTGACTAACTGCGCC
CTGTGGGATCGTCCAATGAGCCGCTCTCTGCACCTGACGGGTGGTATTACCAAAGCA
GCGAACCAGCGTTACGCCACCATTCACGTACCGGATCATGGTCTGTTCGTTGGTGAC
TTTGTAAATTTCTCTAATTCTGCAGTTACCGGTGTGTCTGGCGACATGACCGTTGCGA
CCGTAATCGATAAGGACAATTTCACCGTCCTGACCCCGAACCAGCAAACCTCTGATC
TTAACAACGCTGGCAAGAACTGGCACATGGGCACTAGCTTTCACAAATCTCCGTGGC
GTAAAACCGATCTGGGCCTGATCCCGTCTGTAACTGAAGTGCACTCCTTCGCGACCA
TTGATAACAACGGTTTCGCTATGGGTTATCACCAAGGTGATGTTGCACCGCGTGAAG
TCGGCCTCTTTTATTTTCCGGACGCATTCAACAGCCCGTCCAACTACGTGCGCCGTCA
GATTCCGTCTGAATATGAACCGGACGCCTCCGAGCCGTGCATTAAGTACTATGACGG
TGTGCTGTACCTGATTACCCGTGGCACCCGTGGTGATCGTCTGGGTTCATCTCTGCAT
CGCTCCCGCGACATTGGTCAGACGTGGGAAAGTCTGCGCTTCCCGCACAATGTTCAT
CACACCACCCTGCCGTTCGCGAAAGTCGGCGATGACCTGATCATGTTTGGCTCCGAA
CGTGCTGAAAACGAATGGGAAGCGGGCGCCCCAGACGATCGCTACAAGGCATCTTA
CCCGCGCACCTTCTACGCGCGTCTGAACGTGAACAACTGGAACGCAGACGATATCG
AATGGGTAAACATCACCGACCAGATCTACCAGGGTGGTATCGTGAACTCTGGTGTG
GGCGTTGGTTCCGTTGTAGTTAAAGATAACTACATCTATTATATGTTCGGCGGCGAA
GACCACTTCAACCCGTGGACTTACGGCGATAACTCCGCGAAAGACCCGTTCAAATCC
GATGGTCACCCTTCTGACCTCTATTGTTACAAAATGAAAATCGGTCCGGACAACCGT
GTTTCCCGCGATTTTCGCTACGGCGCTGTTCCAAACCGTGCAGTTCCGGTATTCTTCG
ACACGAACGGCGTGCGTACCGTTCCGGCTCCGATGGAATTCACCGGCGACCTGGGT
CTGGGCCACGTAACCATTCGTGCCTCCACCAGCTCTAACATCCGTTCCGAAGTACTC
ATGGAAGGTGAATACGGCTTTATCGGTAAGTCTATCCCGACGGACAACCCGGCAGG
TCAGCGTATCATCTTCTGCGGCGGTGAGGGTACCTCTAGCACCACCGGCGCGCAAAT
CACCCTGTACGGCGCTAACAACACCGACTCTCGTCGTATCGTATACAACGGTGATGA
ACATCTGTTCCAGTCCGCAGACGTGAAACCGTACAACGACAACGTCACCGCACTGG
GTGGTCCATCCAACCGTTTCACCACTGCGTACCTGGGTTCCAACCCGATCGTTACTA
GCAATGGTGAACGCAAAACTGAACCGGTAGTGTTTGACGACGCTTTTCTGGACGCAT
GGGGCGATGTTCATTACATCATGTATCAGTGGCTGGATGCCGTGCAGCTGAAAGGTA
ACGACGCGCGTATCCACTTTGGTGTGATCGCACAGCAGATTCGCGATGTCTTCATCG
CACACGGTCTGATGGATGAAAATAGTACTAACTGTCGCTATGCGGTGCTGTGCTATG
ACAAATACCCGCGTATGACCGACACCGTGTTCTCGCACAATGAGATTGTTGAACATA
CCGATGAAGAAGGTAACGTGACTACTACCGAAGAACCGGTTTATACCGAAGTGGTT
ATTCACGAAGAAGGTGAAGAATGGGGCGTGCGTCCTGATGGTATCTTTTTCGCGGAG
GCAGCGTACCAGCGTCGCAAACTGGAACGCATCGAAGCTCGTCTGTCGGCACTGGA
ACAGAAA
K5 (SEQ ID NO: 107)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGCCTAAAACCGAAGGTATCCTCCATAAAGGTCAGAGCTTATACGA
ATATCTGGATGCCCGTGTTCTTACTTCTAAGCCATTCGGTGCAGCGGGTGATGCAAC
GACCGACGACACGGAGGTTATCGCTGCGAGCCTGAACAGCCAGAAAGCTGTTACCA
TCTCTGACGGCGTTTTCAGTTCTTCTGGCATCAACTCCAACTACTGTAACCTGGATGG
TCGCGGATCCGGTGTGCTCAGCCACCGTAGCTCTACTGGTAATTACCTGGTGTTTAA
CAATCCGCGTACTGGTCGTCTGAGCAATATCACTGTTGAATCTAACAAAGCGACCGA
TACCACTCAGGGCCAACAGGTGTCCCTGGCAGGTGGCAGTGACGTGACCGTGTCAG
ATGTCAACTTCTCCAACGTGAAAGGCACTGGTTTTAGCCTGATTGCCTACCCAAACG
ATGCTCCGCCGGATGGCCTGATGATCAAAGGCATTCGCGGATCTTACAGCGGTTACG
CGACCAACAAAGCAGCTGGTTGCGTCCTGGCGGATAGCTCCGTTAACAGCCTGATC
GACAATGTGATCGCTAAGAATTACCCGCAATTCGGTGCTGTTGAATTAAAGGGCACT
GCAAGCTACAACATTGTATCGAACGTTATCGGTGCGGATTGTCAGCACGTGACTTAC
AACGGCACTGAGGGACCGATCGCTCCTAGTAACAATCTGATCAAGGGCGTTATGGC
GAACAACCCGAAATACGCGGCAGTTGTGGCGGGTAAAGGCTCGACGAATCTGATCT
CTGATGTACTGGTAGACTATTCTACCAGCGATGCTCGTCAGGCGCATGGTGTTACCG
TCGAAGGATCTGATAACGTGATTAACAACGTACTGATGTCCGGTTGCGACGGAACTA
ATTCCCTGGGTCAGCGTCAAACCGCAACTATCGCGCGTTTCATCGGTACTGCAAATA
ACAACTATGCTAGCGTGTTCCCATCCTATTCTGCCACTGGTGTGATCACGTTTGAGTC
TGGCAGTACCCGTAACTTCGTCGAGGTTAAGCATCCGGGCCGTCGCAACGATCTTCT
GTCATCGGCAAGCACGATTGACGGCGCTGCGACCATCGACGGGACTTCTAACTCTA
ACGTAGTACACGCGCCTGCTCTGGGCCAATACATTGGCTCCATGAGTGGTCGCTTTG
AATGGCGTATTAAGTCAATGAGCCTGCCGTCCGGCGTACTCACTAGCGCGGATAAAT
ACCGTATGCTGGGTGACGGTGCTGTTAGCCTTGCTGTTGGCGGAGGAACTAGCAGTC
AGGTGCGCTTGTTCACCTCAGACGGTACTTCTCGCACTGTTTCTCTGACCAATGGTAA
CGTGCGCCTGAGCACGTCCTCTACTGGCTATTTACAGCTGGGTGCAGACGCAATGAC
TCCGGACTCCACTGGTACTTACGCGTTAGGCTCCGCATCTCGTGCTTGGAGTGGCGG
ATTCACTCAGGCAGCATTCACCGTTACTTCTGACGCACGTTGCAAAACTGAGCCTTT
AACCATCTCTGACGCTTTACTGGATGCTTGGAGTGAAGTGGACTTTGTCCAGTTCCA
GTATCTGGATCGTGTTGAAGAGAAAGGTGCTGACTCCGCGCGTTGGCATTTCGGAAT
CATCGCCCAGCGTGCTAAAGAGGCATTCGAACGTCACGGCATCGATGCGCATCGTT
ACGGTTTCTTATGCTTTGACTCTTGGGACGATGTGTACGAAGAGGATGCAAATGGAT
CTCGCAAACTGATCACTCCGGCGGGTAGTCGCTATGGTATTCGCTATGAGGAAGTTC
TGATCCTCGAAGCAGCGCTGATGCGTCGCACGATCAAGCGCATGCAGGAAGCACTG
GCTGCGTTACCGAAG
STF-37 (SEQ ID NO: 108)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGGAGTTATCTGGAGAGCACGGGTCGTTTTTGATTGGCGGAGTAATT
GATTGTTACTCAACCGTTTCAGATCTTATTTCTTCCTCCCCATCCGTTGGTAGAGTAT
GCAGGACTATAGGGTATTACAGCCCAGGTGATGGAGGTGGGGCAGATTACATAATT
AGTATTGGAACTCCGATGCAAGATTTTAGCGATTCTGGTTCTATAGTTATAGATGAA
TGCAAGTTCGCTAAATTAATCCAGCAAAGCCAATATGATTTAAAGCAGTTTGGAGTA
AAACCATCTGACCCGTCTTATGCAGAAAAAAACGACATATTTATCTCGCAAGCCATT
ACTAGGTCTAGAGTTGGAAGATGCAAGATTATTATAAGCGATGTTATATATCATAAA
AAACCTTTAATTTTTGATTATTACAATCATATGGAAGGAAGTTGTATTGGTAGTGAC
CCGGAATTTACTCCTAGGTTTATAAAAATAGATAATACAACTAGCGGTTTGCCAGAT
ATGGGATACCCTGGTGTTGCTGATGTTGTATCTTACGATGTTGATGCAGGAATAATA
ATTAAAAGACAGAATTCTGGCACAAGTTTTGCCAGAGGTTTCATAATTAAGGGGTTT
CTTCTTCAGTCGGAGAAGAAATCAGCATGGGCAATTTACGCGCCGCATATGGCGGAT
TTTGATATAGACATTGATAGTCGTGGGTTTAATGGAGGAATCAGATGGTTTGTTAAT
TTTCTTGGAAGAATGGCAGGAAGACATATAGGTCTTGGTGCAAACTCATCAGATCCA
ACATTATCTATAGGTGCGTGGTGTTCGAAATTCTCTACAATACCTGATTGTGGTAATT
CCGTTGTATTCAGATTGTCATTCAATGGATTTAACAGAGGTATGCAAATGGAGTATT
TTGGTAATGGGGTTTTAGATAGAGTAACTCTTGAAAATATTTCAAAACCAACACCTA
CGTCGCCAACAACACATGGAATATATGCAACTGATACATGGTTAACTGGCCAGGTGT
CATGTGAAAGTTCTTCAACCTGCATCATCCGTGCTGGCAATAACGCGAACTTCGATA
TTACCCTTAGTGCGGTATTCCATGTTACGCAAGATGATCCTTCCGAGGGTATTGTTCA
TGTATTAAATGGAGGCCGCCTAACTCTGCGTTCATCTACAATTCTTGCTGATTTGGCA
GATACAAAAATCATTAATGAGAATGGAGGTTATCTCGATATTGCCGCAAATACCAG
AACAGGAAATATTGTTTATTCCAATAGTGATAATTACAGATTCAAAGACAGAACCAT
TGGTTTTGGTCAGACTGCGGCAACTACAAAAACAAGCTTCTCTTCTGGTGAAGAGAT
TACATTTTCACTACTAAACGGAACGCCAAAAGCGAATCTATCTGGCGGAACGATCCA
GTTTAACTCTCCATGCCTGATTAAAATCACTGTGCAGGGGAGGGGTATAACATCAGG
AGCACTTACTTTTGGGATAAATGGAGAATCTTCAGAGAGCGTGAGTCAGGGACAGC
AGGTTTCTATGGTTGTCGGAGTGGTATCCGGTGACATTCTTAACCTGAAGGCAACCT
CATCACTGACGCTGGGTAGTGCAGGAGGGGTGCGGGTACTTCTTGAGCCTGTAAAC
1JL (SEQ ID NO: 109)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGggctacaaagttcagagcttagcaattctgtccgacacccaagctgtccacgatgctactaacaccattaaaa
cccagacggacaagatcaaggcagacacgcaggcaatcaaaactcaaacaaatcaaattaaaaccgaaacgggcgtaattcgtgataaa
gcgaacactgcgaaaactgatgcgcaggccgcgagcgccgccgcacaaggcttccgtgatcaggcgaaggagtgggcacaaagtgta
aacgctgataacttattaaccaaaacgggcaacttagctggcctgactgacaagagcgcggcacgttctaatttagggctaggAAGCG
TAGCAACGGAAAACACCGTTCCAATTAAGAAAGGCGGCACTgcggcaacgaccgtcgcggcggc
acgctccaatttagggctgggtagcgttgcaacggagaacactgtcccaattgaaaagggggggactgcggcgacaaccgccgcgaaa
gcgcgtagcaatctgggtttaggtagcgtagctacggagaataccgtgccgattgaaaagggcggcacggcggcgaccactgccgctaa
agcccgttcgaacttcggcttaggcgataacaacaaagtaaaacttggtacactgcgcctgaacgggggtgaatctctggttttcaacgatgt
ggaacgcaatggcctgattatcagcaacgccagatcggtatcgatagctgggttggtcaaaccatgcacaaatggtataccgattggacgc
gtgctggcttagtgcgtgcaggtgacgcgcatctgagcgattatcgtgtgcatgtttggaaagacggtttcaccgaagccctgtttcgtttcct
gccggacgggcgcttgatttccggcaactccggtaatccgtctgttaacgaatttcaaaaagccccgctgtctgatcgtgacctgaaaaaag
aaatcaagtacactgatggcgaagaatcctataaccgtgttcgccaatggcttccggctatgttcaaatacaaagagagcgacgttcagcgtt
acggcctgattgcacaagatctggcacgtattgatccggaatacgttcacttattaccgggctatgcaatctacgaagacgttaagggtgtag
acgaagagggcaatgaggttgttgtggatcgtaaagagatcggctataccgacgatgtgttatctctggattctaacgtcttattaatggatttat
gcgcggcattcgtgcatttattacataaagttgaaaaattggaaggcaaa
STF-48 (SEQ ID NO: 110)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGCAGTTAGAAAGCGATGCTGATGGAATGGGAGATGCACTAGTTGC
AGTTAAGCAGCCATATATCGGCTCAATAGCTTTAACTCAACATGATAAAAATACCAA
CTTCATTTCAGCCAAGGATTTCGGTGCAACAGCTGACGGAACTCTGCATCCACTCAG
CGAGAAATTCTCCACACTATCAGCGGCGCAGGCTGTTTATCCATTCGTAACATCACT
AACTCAGTCTCTTGACTATGCAGGCATACAGGCCGCAATTAATACAGGGCGGAATGT
ATTATTGACATCTGGAACTTACTTCGTAAATGCAACGATAGAGATGAATTCAAACTG
CACAATAAATGGCGAAACAAACAGCAACATAAATAGGCCGGAAACTTTCATAGCAG
TAATAGGAAATATAGCTTGTTTCCATTACCACGCAGCGTTTAATACAATAAATATTG
AAAATGTCTATATTTTTTACGATGGAGGACGCCCTACATCACCTACTGGCAATGATG
GTAAAATTGGCATTCTAATTGATGGAGGAACTACTTCACCAGGCGTTATGCACATTA
AAAATGTTGAGGTTGATGGTGCATGGTGGGCCATATATGATGACTCTGGAAATTACC
TAACAAAGTATACCCAGGTATGGGCGAGGAGAGTTGCGCATGGTTTCTATAAGGCG
AACGGAACGACAATACAGTGGGATACATGTTATGTGCTGGATGCAGCACAGGCATG
GTATGTTGTAAATTGCCTGTCTCCTCAGCTAATAAACTGTGCAGGAGACCAGATCAC
AGTTGACGGGTCGCAATATACATTTGATTCCTCAGGGTTATATTTTTCTGGATGTAAG
TGTCTTACTATTACAGGGTATGATGGTGAGTCTAATATAATAAAAAATACAAATGGA
ATTACTGCGTCGTATATAAAACTTAATGATACTATTGCCCATATATCAGGATTGGCC
GGGCATGGAAACTCAATGCAAACAACGGGGAGTGGGACAGCAGCATTTATCTTTGC
AACAGGCACAAGCATTGTTAACATAAAATCAAGTACCGATAGCTTCCTTGATAGCG
AATCAATAACCTACACTGGCTCTGGATACCCAAACACATTGCTGACAGACTCAACA
GCAAAAATAATTGCTGAGGGATGCCGGTTTAAGGCTCCGACTGGTGGGACTCCTGTA
ATATCAACTTACAGCACAGGGAATGGAGTATTTACTGACTGCTCATTAACTGGGACG
CAAACTTCAGGCTCATATGTTGAATCACGAAGCTCTGCAGGTAATCAGTTGCCAGCA
GTGTACACAGCGAAAGGAACTCAGGCTGTTGCAGCTAACGTAGCAACTACGTTGTTT
GAACTGCCAAATAGCCAAGGGATGTACCTGATAAGCGTTTGGGCAGAAAGCAGTGG
AACAAATTTCTCTTCGCTTCAGCTTGCCATGTGGGACGGAACAACACTTACTTTAAC
TCCGCTTAAGTCAGGAGGGTTGATATCATTTACAGTGACAGGAAGGATTGTAACCAT
CACAAGCCAGGGAACAACAACATTTAACTGGACATACACCAAGGCAGGG
STF-49 (SEQ ID NO: 111)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGGGGGCTATTGGTGATGGTGTTCATGATGATACATCAGCTCTATCA
GAATTACTTTCTGTTGCAACAGGTGGTGAAAAGATAGATGGGCGAGGGCTTACTTTT
AAAGTATCAACTCTTCCAGATGTCAGTCGATTTAAAAATGCTCGTTTTTTATTTGAGA
GAATACCGGGTCAGCCTCTTTTTTATGCTTCTGAAGATTTTATCCAGGGAGAGTTATT
TAAAATTACAGATACACCGTGGTACAACGCCTGGACGCAGGATAAAACGTTTGTAT
ATGACAATGTCATCTATGCGCCTTTTATGGCTGGAGACCGCCATGGTGTAAATAACC
TCCATGTTGCATGGGTTCGCTCAGGAGATGACGGGAGGACCTGGACAACGCCGGAA
TGGCTTACAGATTTACATGAAAACTATCCCACAGTTAACTATCACTGCATGAGTATG
GGGGTTGTCAGAAATCGCCTTTTTGCTGTAATTGAGACGCGGACCGTGAGCGGAAAT
AAACTGCAGGTTGCAGAGTTGTGGGATCGCCCAATGAGTCGCAGCCTTCGCGCTTAT
GGTGGTATAACGAAAGCAGCAAATCAGCAAGTCGCTTATATTCGCATTACTGATCAC
GGATTATTTGCTGGTGATTTTGTCAACTTCTCAAACTCTGGTGTTACAGGTGTTACCG
GGAATATGACGGTGACTACTGTTATTGATAAAAATACTTTTACAGTTACGACGCAAA
ATACCCAGGATGTGGATCAGAATAACGAGGGTAGATACTGGAGTTTTGGTACATCA
TTTCACTCGTCACCATGGAGAAAAACCAGTCTTGGAACTATTCCTTCTTTTGTTGACG
GAAGCACTCCTGTTACTGAGATTCACAGTTTTGCGACGATTAGCGATAACAGTTTTG
CTGTTGGCTACCATAATGGTGATATTGGTCCACGCGAGCTTGGGATACTCTATTTCTC
TGATGCTTTCGGTTCTCCTGGTAGCTTTGTTCGCAGACGCATACCTGCAGAATATGA
GGCGAATGCATCTGAGCCATGTGTAAAATATTATGATGGCATTCTGTATCTGACGAC
CAGGGGGACATTAAGTACTCAACCCGGTAGTTCATTGCACAGAAGCTCTGATTTAGG
TACATCATGGAATTCTCTTCGCTTCCCAAATAATGTTCATCACTCAAACCTTCCTTTT
GCCAAAGTTGGCGATGAGCTGATTATTTTTGGCAGTGAGCGCGCATTTGGTGAGTGG
GAAGGAGGAGAACCTGATAACCGTTATGCAGGAAACTATCCAAGAACATTTATGAC
CAGAGTTAACGTCAATGAGTGGAGTCTGGATAATGTAGAGTGGGTTAATGTTACTGA
TCAGATTTATCAGGGCGGAATAGTTAACTCTGCGGTTGGTGTTGGTTCAGTTTGTATC
AAAGACAACTGGCTGTACTACATTTTCGGTGGGGAAGACTTTCTAAACCCATGGAGC
ATAGGGGATAACAACAGAAAATATCCTTATGTTCACGATGGTCACCCGGCTGATTTG
TATTGTTTCAGGGTGAAAATTAAACAGGAAGAATTTGTTTCAAGGGATTTTGTCTAC
GGAGCCACTCCTAACAGAACGCTTCCTACTTTTATGTCGACGTCAGGCGTGAGGACG
GTTCCTGTACCCGTTGATTTCACAGATGATGTTGCCGTCCAGTCACTGACTGTCCATG
CAGGTACATCAGGACAAGTTCGCGCGGAAGTCAAACTTGAGGGTAATTACGCCATT
ATTGCGAAGAAAGTACCGTCTGATGATGTTACCGCTCAGAGATTAATCGTTAGCGGC
GGTGAAACAACGTCTTCAGCAGATGGTGCAATGATAACGTTGCATGGTTCCGGAAG
CAGTACTCCTCGTCGCGCGGTATATAACGCACTCGAACATCTTTTTGAGAACGGAGA
TGTTAAACCTTATCTTGATAATGTAAATGCTCTTGGTGGTCCGGGAAACAGGTTCTC
GACAGTTTATCTTGGCTCCAATCCTGTGGTTACCAGTGACGGAACATTAAAGACAGA
GCCGGTCTCTCCTGACGAAGCATTGCTGGATGCCTGGGGTGACGTCAGGTATATCGC
TTATAAATGGCTGAACGCTGTCGCTATAAAGGGGGAAGAAGGGGCGAGGATACATC
ATGGTGTAATCGCGCAGCAACTTCGTGATGTTCTTATTTCTCACGGACTCATGGAAG
AAGAAAGCACAACATGCCGCTATGCGTTTCTTTGCTATGACGATTATCCCGCAGTAT
ATGATGACGTCATTACTGGCCAAAGGGAAATGCCGCTGACTGATAATGACGGGAGC
ATCATTGTTGATGAGGATGATAATCCAGTGATGGTAATGGAAGACATCATTGAGCGC
GTTGAAATAACGCCAGCAGGATCTAGATGGGGGGTCAGACCTGATCTCTTATTCTAT
ATCGAGGCGGCATGGCAGCGCAGAGAAATAGAAAGAATAAAAGCTAGGTTAGACTT
AATAGAAGGGAAGCAC
STF-52 (SEQ ID NO: 112)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGCAGCTAGCAAGCTCAGAAGATGGAATGGGTGACGCACTAGTTGC
AGTTAAGCAGCCATATATCGGCTCAATAGCTTTAACTCAACATGATAAAAATACCAA
CTTCATTTCAGCCAAGGATTTCGGTGCAACAGCTGACGGAACTCTGCATCCACTCAG
CGAGAAATTCTCCACACTATCAGCGGCGCAGGCTGTTTATCCATTCGTAACATCACT
AACTCAGTCTCTTGACTATGCAGGCATACAGGCCGCAATTAATACAGGGCGGAATGT
ATTATTGACATCTGGAACTTACTTCGTAAATGCAACGATAGAGATGAATTCAAACTG
CACAATAAATGGCGAAACAAACAGCAACATAAATAGGCCGGAAACTTTCATAGCAG
TAATAGGAAATATAGCTTGTTTCCATTACCACGCAGCGTTTAATACAATAAATATTG
AAAATGTCTATATTTTTTACGATGGAGGACGCCCTACATCACCTACTGGCAATGATG
GTAAAATTGGCATTCTAATTGATGGAGGAACTACTTCACCAGGCGTTATGCACATTA
AAAATGTTGAGGTTGATGGTGCATGGTGGGCCATATATGATGACTCTGGAAATTACC
TAACAAAGTATACCCAGGTATGGGCGAGGAGAGTTGCGCATGGTTTCTATAAGGCG
AACGGAACGACAATACAGTGGGATACATGTTATGTGCTGGATGCAGCACAGGCATG
GTATGTTGTAAATTGCCTGTCTCCTCAGCTAATAAACTGTGCAGGAGACCAGATCAC
AGTTGACGGGTCGCAATATACATTTGATTCCTCAGGGTTATATTTTTCTGGATGTAAG
TGTCTTACTATTACAGGGTATGATGGTGAGTCTAATATAATAAAAAATACAAATGGA
ATTACTGCGTCGTATATAAAACTTAATGATACTATTGCCCATATATCAGGATTGGCC
GGGCATGGAAACTCAATGCAAACAACGGGGAGTGGGACAGCAGCATTTATCTTTGC
AACAGGCACAAGCATTGTTAACATAAAATCAAGTACCGATAGCTTCCTTGATAGCG
AATCAATAACCTACACTGGCTCTGGATACCCAAACACATTGCTGACAGACTCAACA
GCAAAAATAATTGCTGAGGGATGCCGGTTTAAGGCTCCGACTGGTGGGACTCCTGTA
ATATCAACTTACAGCACAGGGAATGGAGTATTTACTGACTGCTCATTAACTGGGACG
CAAACTTCAGGCTCATATGTTGAATCACGAAGCTCTGCAGGTAATCAGTTGCCAGCA
GTGTACACAGCGAAAGGAACTCAGGCTGTTGCAGCTAACGTAGCAACTACGTTGTTT
GAACTGCCAAATAGCCAAGGGATGTACCTGATAAGCGTTTGGGCAGAAAGCAGTGG
AACAAATTTCTCTTCGCTTCAGCTTGCCATGTGGGACGGAACAACACTTACTTTAAC
TCCGCTTAAGTCAGGAGGGTTGATATCATTTACAGTGACAGGAAGGATTGTAACCAT
CACAAGCCAGGGAACAACAACATTTAACTGGACATACACCAAGGCAGGG
1AR (SEQ ID NO: 113)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGatcgctacccgcgtgtccaaagaaggtgacactatgactggtaagctgactctgtctgcgggtaacgatgcg
ctggtgctgactgcgggcgagggcgcgtcctcgcacattcgctctgacgtgggcgggacgaacaactggtatatcggtaaaggcagtgg
ggataacggtttaggcttctactcatacatcactcagggcggggtgtatattaccaacaacggggaaatcgctttaagcccgcagggtcagg
gtacgtttaacttcaaccgtgatcgtctgcacatcaacggcacgcaatggacggcacatcaaggcggtggctgggaaaaccagtggaatca
ggaagcgccgatttttattgatttcggcaacgtgggcaatgatagctactacccgattatcaaaggtaagtccggcattaccaacgaaggttat
atttctggcgtggacttcggtatgcgtcggattactaacacgtgggcgcagggtattatccgcgtaggcaatcaggaaaacggtagcgatcc
gcaggccatctacgagttccatcataatggcgtactgtacgttcctaatatggtaaaaacgggtgcgcgtctgagcgcaggtgggggggat
ccggtatggcagggtgcatgtgttgttatcggtgacaatgacacgggcttagtgcatggtggcgatggtcgcatcaatatggttgcaaacggt
atgcacattgcgtcttggagttccgcgtatcatttacatgagggtttatgggatactacgggcgcgttatggacggagcaagggcgtgcaatt
atcagatcggtcatctggtacaacaaagcgatgcctattccacctttgtccgtgatgtatacgttcgttcggatattcgcgttaaaaaagatctg
gtgaaattcgaaaacgctagcgaaaaactgtccaaaatcaacggttatacttatatgcagaaacgcgggttagacgaagaaggtaatcaga
aatgggagcctaacgccggattaatcgcgcaggaagtgcaggcgattctgccggaactggtagaaggcgatccggacggtgaagcatta
ttacgtctgaactacaatggcgtgatcggcctgaatactgcggcgattaatgaacatacggcagagatcgcggagctgaaaagcgagattg
aagaactgaaaaaaattgtcaaaagcctgttaaag
1AR-AP1 (SEQ ID NO: 114)
atggcagtaacaggaccgtgggtaggatcgtctgcagtagttaatacaggacaaaattggatggtcggcgcggcccaacgattaagaatg
ggtgctccgttctggatgagcaacatgattgggcgctctgttgaagtgattcatacgttaggcgcagatcataattttaatggtcaatggtttcgt
gaccgttgctttgaggcgggcagtgcgccgatcgtgtttaacatcactggcgatttagtttcttactcccgtgacgttccgctgtttttcatgtatg
gtgacacgccgaacgagtatgtacaattaaacattcacggtgtcacgatgtacgggcgcgggggcaacggttgggcggcgggtgcaatc
ggtgcgagcgatggcggggtgtgcatccagaatgatattggaggccgactgcgtatcaacaatggtggggcaatcgcgggcggtggcg
gtggtgggggtggttattctcaggctaacaattgggcaggtaagtacgtttgcggtggcggtggcggtcgtccgttcggcttaggtggcaac
aacggtgcgcgttggcctgggggcaacgctagcctgacctcgccgggcgcaggtgggaacactggcacgcgttattacgctggcgggg
gaggtgaggttggtcagccgggtcagtatgcaaaccccggcgcgggttactccaccccaccaacgtcgccgggcgcggcagttgcaggt
agtgcgccaacttggcaaaacgtgggcgctatttatggcccgcgtgtttaa
1AR-AP2 (SEQ ID NO: 115)
ATGAGTGAACAGACCATCGAACAAAAATTAAGCGCGGAAATCGTGACTCTGAAAAG
TCGCATTCTGGATACTCAGGACCAGGCAGCACGTCTGATGGAAGAGTCTAAAATCTT
GCAGGGCACTCTGGCAGAAATTGCCCGTGCGGTGGGTATCACAGGCGACACGATCA
AAGTAGAAGAAATTGTGGAGGCCGTAAAGAATCTCACAGCGGAGAGCACCGATGA
AGCAAAAGACGAAGAATAA
13-13.0 (SEQ ID NO: 116)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGATCATCCAGTTAGAAGATAGTCAAGGCGCCCATTTTTCCACTGAA
CGTACTTTAGCGACAGGTGCAATTAAAACTCGTTTCTTTGGCGAAACATTTACTGAT
GGTACATTATACCTAAATCAGATGAATAATAGTTCTGAACGATTCTCTATTAATAAT
TGGGGAAATTCAGAAGTTGGTCGCCCGGCAGTGTTGGAAGTCGGTGATTCCAAAGG
TTATCACTTCTATACGGAACGCGGGACAGATAACAGTTTGAATTTTGATGTTGCTGG
CAATTTTACTGTGCATGGACCTTCCGGGATTACTATCAAAACCTCTACTGGTGCTCGC
CATATCTGGTTTAGAGATGATAGCGATGCAGAAAAGGCTGTTATCTGGGCTACAGAT
GAGGGTATTTTACATATACGAAATAATTATGGGGGTTCATTTAGTCATCACTTCCAG
GGTGCAATGATTCTAGCGGGAGAGCGTGTTCCATATAATAGTGAATACGCTCTTATC
CGTGGTAATATTTCCGGTGGTGCATGGGTAGACTGGCGAGGTCGTCCGGCTGGATTG
TTGGTAGACTGTCAGGACTCACGAAATCAAGCATATAACATTTGGAAAGCTACTCAT
TGGGGCGACCAGCACCTTGCGGCGATGGGTGTTCATGCTGGCGGTGGTAATCCTCAG
GTTGTATTGCATGTGGGTGGGAATGATTATGCATTTGCATCTAACGGTGATTTTACTG
CTGGTGCTGCTGTATATTGTAACGACGTTTATATTCGTTCTGACCGTCGTCTGAAAAT
TAATGTTAAAGACTACGAAGAGAATGCGGTGGATAAGGTAAATAAACTCAAAGTTA
AAACCTATGATAAAGTTAAATCTCTTTCTGACCGCGAAGTTATCGGCCATGAGATTG
GTATTATCGCACAGGATTTGCAAGAAGTATTACCGGAAGCTGTTAGCACTTCTAGTG
TCGGATCTCAGGATAACCCAGAAGAAATTTTAACAATTTCTAACTCTGCTGTGAACG
CGCTTTTAATTAAGGCTATTCAGGAAATGAGTGAAGAAATTAAAGAATTGAAAACG
CCTCTCTTTACTAAAATTGCTCGCAAAATTAGTAAATATTTTAAATTCTAA
13-13.0-AP1 (SEQ ID NO: 117)
ATGGCAGTAGTTGGAGTTCCTGGCTGGATTGGAAGTTCAGCCGTAAATGAAACGGG
TCAGCGCTGGATGAGTCAAGCAGCTGGTCAATTAAGATTGGGTGTTCCTTGCTGGAT
GAGTCAATTTGCAGGTCGCTCAAGAGAAATTATTCATACACTTGGAGCAGACCATAA
CTTCAATGGTCAATGGTTCCGAGATAGATGTTTTGAGGCAGGTAGTACACCTATAGT
GTTTAATATCACTGGAGATTTAGTATCATATTCTAAAGATGTTCCTTTATTCTTCATG
TACGGAGATACACCGAATGAATATGTTCAACTGAATATACACGGCGTAACGATGTA
TGGACGTGGCGGTAATGGCGGTAGCAATAGTCCTGGTTCAGCTGGAGGTCATTGTAT
TCAAAACGATATTGGTGGGAGACTAAGAATTAATAACGGTGGAGCTATTGCCGGCG
GCGGCGGTGGCGGCGGTGGCGGTAGATATGGCAGACTATCATTTGGTGGTGGCGGT
GGTCGCCCATTCGGTGCTGGCGGGTCTTCCTCTCATATGAGTTCCGGTGCAACTGCT
GGCACCATTTCCGCTCCGGGTGCAGGATCTGTCGGTGAGGGaTCTCTTTGGGTATATA
CAGGCGGTTCGGGTGGTAATGTCGGTGCTGCTGGAGGAAGATGTAATATTCAAGGT
AACGGTACAGAATATGATGGCGGTGCTGCTGGTTATGCTGTTATAGGGTCTGCTCCA
ACTTGGATAAATGTTGGAGCAATATATGGTCCAAGAGTATAA
13-13.0-AP2 (SEQ ID NO: 118)
ATGTCTGAACAAACTATTGAACAAAAACTGTCTGCTGAAATCGTAACTCTGAAGTCT
CGTATCCTTGATACGCAGGACCAAGCGGCTCGTCTGATGGAAGAATCCAAAATTCTG
CAAGGAACTTTGGCTGAAATTGCTCGTGCAGTAGGTATCACTGGCGATACTATCAAA
GTTGAAGAAATCGTTGAAGCTGTCAAGAATCTTACTGCTGAATCTGCAGATGAAGCA
AAAGATGAAGAATGA
5) INSERTION POINT SAGDAS
13-14.3 (SEQ ID NO: 119)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACA
GAACTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGA
ACACGGTGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTG
GAGTACGGTCAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCA
CGCCGGGACCATCACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATT
TTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTT
GAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAGTA
CGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTATTTCTGATGATATTGGA
TGGATGCATTATATTCAACGAAATAAAGATAATACAGTTGAAGCCGTATTAAAT
GGTCAACAGACAATTAACGAAAATATTATTGCGAAAAAGGATATTTGGGTTGAC
CGAGCAGTTCACACCCTTGGCGAAATCACTACAAATGCTGTTAATGGTCTTCGT
ATTTGGAATAATGATTATGGAGTCATTTTTAGACGTTCAGAAGGAAGTCTTCAT
ATTATTCCTACCGCATTTGGTGAAGGAGAAACCGGTGATATTGGACCTTTACGT
CCTCTCAGTATAGCTTTAGATACCGGTAAAGTTACTATTCCGGATTTACAATCA
AGTTACAATACGTTCGCTGCTAACGGTTATATTAAATTTGTTGGTCATGGAGCG
GGGGCCGGCGGTTATGACATTCAATATGCTCAAGCGGCTCCTATTTTCCAGGA
AATCGATGATGATGCTGTAAGCAAATATTATCCTATTGTTAAACAGAAGTTTTT
AAACGGTAAATCCGTTTGGTCTTTAGGTACCGAAATTGAATCAGGTACATTCGT
TATTCATCATCTGAAAGAAGATGGTTCACAAGGCCATGCGTCTCGTTTTAATCA
AGACGGTACTGTTAACTTCCCGGATAACGTTCTGGTCGGCGGTGATATTAACAT
GAAAGGCATGATGACTTTTGACGCCGGACGTTTAGGATCACGAGATTATTTTAA
ATTTAACCATTGGGGTGATAGTAATAATGGTCGTGATAACATCATCCAGTTAGA
AGATAGTCAAGGCGCCCATTTTTCCACTGAACGTACTTTAGCGACAGGTGCAAT
TAAAACTCGTTTCTTTGGCGAAACATTTACTGATGGTACATTATACCTAAATCA
GATGAATAATAGTTCTGAACGATTCTCTATTAATAATTGGGGAAATTCAGAAGT
TGGTCGCCCGGCAGTGTTGGAAGTCGGTGATTCCAAAGGTTATCACTTCTATAC
GGAACGCGGGACAGATAACAGTTTGAATTTTGATGTTGCTGGCAATTTTACTGT
GCATGGACCTTCCGGGATTACTATCAAAACCTCTACTGGTGCTCGCCATATCTG
GTTTAGAGATGATAGCGATGCAGAAAAGGCTGTTATCTGGGCTACAGATGAGG
GTATTTTACATATACGAAATAATTATGGGGGTTCATTTAGTCATCACTTCCAGG
GTGCAATGATTCTAGCGGGAGAGCGTGTTCCATATAATAGTGAATACGCTCTTA
TCCGTGGTAATATTTCCGGTGGTGCATGGGTAGACTGGCGAGGTCGTCCGGCT
GGATTGTTGGTAGACTGTCAGGACTCACGAAATCAAGCATATAACATTTGGAAA
GCTACTCATTGGGGCGACCAGCACCTTGCGGCGATGGGTGTTCATGCTGGCGG
TGGTAATCCTCAGGTTGTATTGCATGTGGGTGGGAATGATTATGCATTTGCATC
TAACGGTGATTTTACTGCTGGTGCTGCTGTATATTGTAACGACGTTTATATTCG
TTCTGACCGTCGTCTGAAAATTAATGTTAAAGACTACGAAGAGAATGCGGTGG
ATAAGGTAAATAAACTCAAAGTTAAAACCTATGATAAAGTTAAATCTCTTTCTG
ACCGCGAAGTTATCGGCCATGAGATTGGTATTATCGCACAGGATTTGCAAGAA
GTATTACCGGAAGCTGTTAGCACTTCTAGTGTCGGATCTCAGGATAACCCAGAA
GAAATTTTAACAATTTCTAACTCTGCTGTGAACGCGCTTTTAATTAAGGCTATT
CAGGAAATGAGTGAAGAAATTAAAGAATTGAAAACGCCTCTCTTTACTAAAATT
GCTCGCAAAATTAGTAAATATTTTAAATTC
13-14.3-AP1 (SEQ ID NO: 120)
ATGGCAGTAGTTGGAGTTCCTGGCTGGATTGGAAGTTCAGCCGTAAATGAAAC
GGGTCAGCGCTGGATGAGTCAAGCAGCTGGTCAATTAAGATTGGGTGTTCCTT
GCTGGATGAGTCAATTTGCAGGTCGCTCAAGAGAAATTATTCATACACTTGGAG
CAGACCATAACTTCAATGGTCAATGGTTCCGAGATAGATGTTTTGAGGCAGGTA
GTACACCTATAGTGTTTAATATCACTGGAGATTTAGTATCATATTCTAAAGATG
TTCCTTTATTCTTCATGTACGGAGATACACCGAATGAATATGTTCAACTGAATA
TACACGGCGTAACGATGTATGGACGTGGCGGTAATGGCGGTAGCAATAGTCCT
GGTTCAGCTGGAGGTCATTGTATTCAAAACGATATTGGTGGGAGACTAAGAAT
TAATAACGGTGGAGCTATTGCCGGCGGCGGCGGTGGCGGCGGTGGCGGTAGA
TATGGCAGACTATCATTTGGTGGTGGCGGTGGTCGCCCATTCGGTGCTGGCGG
GTCTTCCTCTCATATGAGTTCCGGTGCAACTGCTGGCACCATTTCCGCTCCGGG
TGCAGGATCTGTCGGTGAGGGaTCTCTTTGGGTATATACAGGCGGTTCGGGTG
GTAATGTCGGTGCTGCTGGAGGAAGATGTAATATTCAAGGTAACGGTACAGAA
TATGATGGCGGTGCTGCTGGTTATGCTGTTATAGGGTCTGCTCCAACTTGGATA
AATGTTGGAGCAATATATGGTCCAAGAGTA
13-14.3-AP2 (SEQ ID NO: 122)
ATGTCTGAACAAACTATTGAACAAAAACTGTCTGCTGAAATCGTAACTCTGAAG
TCTCGTATCCTTGATACGCAGGACCAAGCGGCTCGTCTGATGGAAGAATCCAA
AATTCTGCAAGGAACTTTGGCTGAAATTGCTCGTGCAGTAGGTATCACTGGCG
ATACTATCAAAGTTGAAGAAATCGTTGAAGCTGTCAAGAATCTTACTGCTGAAT
CTGCAGATGAAGCAAAAGATGAAGAA

T4-like SEQUENCES (underlined are the DTF insertion sites used in the fusions described above):
WW13
(SEQ ID NO: 123)
MATLKQIQFKRSKTAGARPAASVLAEGELAINLKDRVLFTKDDQGNIIDLGFAKGGSIDGNVIHIG
NYNQTGDYTLNGTFTQTGNFNLTGIARVTRDIIAAGQIMTEGGELITKSSGTAHVRFFDGNSRE
RGIIYAPANDGLTTQVLNIRVQDYAAGSESTYAFSGSGLFTSPEVSAWKSMSTPQILTDKVITNG
KKTGDYDIYSLSNNTPLAESETAINHLRVMRNAVGAGIFHEVNVNDGITWYSGDGLDTYLWSFN
WAGGLKAGHSISVGLPGGSKGYSELGTASIALGDNDTGFKWHQDGYFHTVNNGTRTFIYGPA
ETQSLRKMVMGYSPDGILMTTPPTENYALATVVTYHDNNAFGDGQTLLGYYQGGNYHHYFRG
KGTTNINTHGGLLVTPGNIDVIGGSVNIDGRNNNSTLMFKGYTMGQSSVDNMYIAVWGNTFTN
PSEGTRKNVMEISDDIGWMHYIQRNKDNTVEAVLNGQQTINENIIAKKDIWVDRAVHTLGEITTN
AVNGLRIWNNDYGVIFRRSEGSLHIIPTAFGEGETGDIGPLRPLSIALDTGKVTIPDLQSSYNTFA
ANGYIKFVGHGAGAGGYDIQYAQAAPIFQEIDDDAVSKYYPIVKQKFLNGKSVWSLGTEIESGT
FVIHHLKEDGSQGHASRFNQDGTVNFPDNVLVGGDINMKGMMTFDAGRLGSRDYFKFNHWG
DSNNGRDNIIQLEDSQGAHFSTERTLATGAIKTRFFGETFTDGTLYLNQMNNSSERFSINNWGN
SEVGRPAVLEVGDSKGYHFYTERGTDNSLNFDVAGNFTVHGPSGITIKTSTGARHIWFRDDSD
AEKAVIWATDEGILHIRNNYGGSFSHHFQGAMILAGERVPYNSEYALIRGNISGGAWVDWRGR
PAGLLVDCQDSRNQAYNIWKATHWGDQHLAAMGVHAGGGNPQVVLHVGGNDYAFASNGDF
TAGAAVYCNDVYIRSDRRLKINVKDYEENAVDKVNKLKVKTYDKVKSLSDREVIGHEIGIIAQDL
QEVLPEAVSTSSVGSQDNPEEILTISNSAVNALLIKAIQEMSEEIKELKTPLFTKIARKISKYFKF
PP-1
(SEQ ID NO: 124)
MATLKQIQFKRSKTAGQRPAASVLAEGELAINLKDRVLFTKDDQGNIIDLGFAKGGSIDGNVIHK
GNYNQTGDYTLNGTFTQTGNFNLTGIARVTRDIIAAGQIMTEGGELITKSSGTAHVRFHDSADR
ERGIIFSPANDGLTTQVVNIRVQDYKASSESTFAFNGNGLFSSPEVFGWKSVSTPVIYTNKVITN
KKVKDDYDIYSMADNVPLSEITTAINHLRVMRNAVGSGIFHEVKDNDGITWYSGDGLDAYLWSF
TWSGGIKSSHSISIGLTPGPKDYSILGPSSIALGDNDTGFKWHQDGYYFSVNNGTKTFLFSPSE
TTSLRKFVAGYSTNGTDLTTPPTENYALATVVTYHDNNAFGDGQTLLGYYQGGNYHHYFRGK
GTTNINTHGGLLVTPGNIDVIGGSVNIDGRNNASTAMFKGNTTGSSSVDNMTISVWGNTFTNPS
EGNRKNVMEISDATSVVMSYIQRLTTGEVEMNVNGSFESSGVTAGNRGVHTTGEISSGAVNAL
RIWNADYGVIFRRSEGSLHIIPTAYGEGKNGDIGPLRPFSIALDTGKVVIPDLESSYNTFAANGYI
KFAGHGAGAGGYDIQYSQAAPIFQEIDDAAVSKYYPIVKQKFLNGKAVWSLGTEINSGTFVLHH
LKEDGSQGHTSRFNADGTVNFPDNVQVGGGEATIARNGNIFSDIWKTFTSAGETTNIRDAIATR
VSKEGDTMTGKLTLSAGNDALVLTAGEGASSHIRSDVGGTNNWYIGKGSGDNGLGFYSYITQG
GVYITNNGEIALSPQGQGTFNFNRDRLHINGTQVVTAHQGGGWENQWNQEAPIFIDFGNVGND
SYYPIIKGKSGITNEGYISGVDFGMRRITNTWAQGIIRVGNQENGSDPQAIYEFHHNGVLYVPNM
VKTGARLSAGGGDPVWQGACVVIGDNDTGLVHGGDGRINMVANGMHIASWSSAYHLHEGLW
DTTGALWTEQGRAIISFGHLVQQSDAYSTFVRDVYVRSDIRVKKDLVKFENASEKLSKINGYTY
MQKRGLDEEGNQKWEPNAGLIAQEVQAILPELVEGDPDGEALLRLNYNGVIGLNTAAINEHTAE
IAELKSEIEELKKIVKSLLK
WW55
(SEQ ID NO: 125)
MADLSRIQFKRTSTKGRRPDASTMNPGELAINLADQYLLTKNDSGAIINLSCPPVYDRDVTMAG
KVKGNNYILSKTANYLEDQTARDLNYFGAFRTNGLDGLLELTLNVPHSSGVQHGRGFTFQYGH
TGSRVETYGYNKEGQKAFSYKMYHEGDKPTPGELNVYSKQEIDRMFVKNVKMVVPSGGATR
GYFKIASAMIPQSGRMAFLRIYGGNGYNVNSYDQVDFLEIVIRSGNNNPKGVSIAAYRRNSLNV
HEVFAINTSGDNYDIYVNYGRFTDNVIVEFGKTVDVALTVHDVPEFSATKPETGTKFDARVITMF
NTENKAGTLMFDNNNQLTYDIVSLSNGPDDVRNYLRKFRSKAGEMIWHETVQGAVYRLATGTT
DSTEVLRVDSNSALPGSYKGYVITGKMELHGSGSAMNLHRQTGQAAYMAVWVDRRDGKNQR
SGYIGHADGTTDGFVWRNDVGANSFDLESSGQVNLTTGKTKIVYTNGQYYSANSDAFRMIYG
NYGAFWRNDGGKVYLLSTAENDRFGGWNGNRPFIYDLSTGKVTLGGDGNEGALVLERDSRA
ARFSNSVFLEKGLLTFSAGGNQSMDSFTINHWGNSNAGRYNVLQFEDTKGTHFTTERNADGG
LLAHFRGDLTTEGKLTWGKGTATSSFNIRAWGNSDSRKQVFECVDESGWHWYTQRPGGPGT
SAIEFAINGTVKPQAIHTGGNILLNGADIEFRRTGNKHLWFRDPNGLELGLIYCDDNGVIRFRGQ
KQGQDWVFANKMIQLGTASTVGGSGNGLIRGQVQGGAWAQWRDRAAGILVDCQQSTDSAH
NIWKATHWGKYHIAAMGVHVPSGTIGNAMARLNVNDANFDFSASGDMSAGRNGSFNDVYIRS
DARLKINKEEYKENATDKVNRLTVYTYDKVKSLTDRTVIAHEVGIIAQDLEKELPEAVTTSKIGDP
DKPEEILTISNSAVNALLIKAFQEMSEELKAVKAELAELKK
WW34
(SEQ ID NO: 126)
MADLSRIQFKRTSTKGRRPDAGTMNPGELAINLADQYLLTKNDSGAIINLSCPPVYDSDVTMAG
KVKGNNYILSKTANYFEDQTARDLNYFGAFRPNNADDWSNLILNIPHPSGKAHGRGFEFQYGS
SSSQVKTYGFDKDGNKRFSFRMYHEGDKPTPGELNVYSKQEIDRMFVKNVKMSTPSGEATRG
YFKIASAMIPQSGRMAFLRIYGGNGFNVNSYDQVDFLEIVIRSGNNNPKGVSIAAYRRNSLNVH
EVFAINTSGDNYDIYVNYGRFTDNVIVEFGKTVDVALTVHDVPEFSATKPETGTKFDARVITMFN
TENKAGTLMFDNNNQLTYDIVSLSNGPDDVRNYLRKFRSKAGEMIWHETVQGAVYRLATGTTD
STEVLRVDSNSAIPGSYKGYVITGKMELHGSGNSMILHRQTAQAAYMSWWDRRDGKNQRSG
YIGHADGTSDAIVWNNDIGQNSAVLETSGQISFRTGATKIVYTNGQYYSANSDAYRMIFGNYGA
FWRNDGTKVYLLSTAENDKYGGWNAYRPFIYDLTSGNVQLGGDGNEDALTLECASRAARFSN
DVYIKKGLLTFDAGRAGSRDYIRFNHWGDSNNARDNVLCIEDSQGRHFSTERAMGTGALKAYF
LGDLEVGGKFTWGKNTATSSFNIRAWGNDSRKQVLECADESGWHWYTQRTGGPDTSAIDFAI
NGTVRPQAIHTGGNITINGADIEFKRTGNKHIWFRDPNGLELGLMYCDDAGAIRFRGQKQAQA
WKFADKMIQLESGTVSGGGNGLIRGEVAGGSWASWRDRAAGLMVGCPQSTNSAHNVWKAT
HWGKYHIAAMAVHVPDGTITNALARLNVHDANFDFSASGDLSAGRNGSFNDVYIRSDARLKINK
EEYKENATDKVNRLTVYTYDKVKSLTDRTVIAHEVGIIAQDLEKELPEAVTTSKIGDPDKPEEILTI
SNSAVNALLIKAFQEMSEELKAVKAELAELKKN
WW14
(SEQ ID NO: 127)
MATLKAIQFKRSKTPGAKPTVDQLVEGELAINLRDRTIFTKSDQNQIIDLGFAKGGQVDGDVTIN
GTLNLNGPEIVASGGYIEFNYRTTGSGSWAGQHAAKAPIFVDLSAALSTSEYNPLFKQRYKDGT
FSAGTLVTEGSFKFHYINEAGDSKYWTFNRNGNFQVDTGSLFVSGGNISASGNINSASGFVSA
PQINTKNIILDTKAFGQYDSQSLVNYVYPGTGETNGVNYLRKVRAKSGGTMWHELCTAQLGQA
DEMSVWVTGNTPQSKQYGVRNDGRUGRNSLALGTMTTDFPSSDYGNTGAMGDKYLVLGDTA
TGLKYIKQGNFDLVGGGYSVASITTDGFRGTSKTLFGRSNDQGLTWLLPGQNSAMVSIRTEIDG
NNSGDGQTHLGYNSNGKLYHYFRGTGRVAISMAEGMIIEPGILNIKTGVNELNLRADGTVSTTQ
RLMVNNGLVLNANNNTSALALTAPTGVDGTKTINWDAGTRNGQNKNTVTMKAWGNSFNAGG
GNRETVFEVSDSQGYYFYGQRTNPASGETVGPINFKFNGSVETGHFSSLGNISASGTGSFGG
NVTMTNGLFVQGGASINGQVKMGGTADALRIWNAEYGMIFRRSETGSSASFHLIPTLQNAGEN
GGISDLRPLSINLASGTVIMGNKSTGGPLFTVDNVSKFVQTDCRLRVNMDSDGIVLNASSQAAS
NFIQGRKADVTKVVYLGIGDGGNVVRMHNYTYSHGIALNSDTVDITKPLKIGSDIRIGTDGNIIGSA
TLDNFKNLNTTLDHKVNMGGWSGGATTGVVYKFATVEIPQATGTASFKIFGGSGFNFKSYGQA
SIAEIILRTGNNNPKGLNATLWNRTSEAISQIASVNTSEDIYDIYVYLGGYSNSLVVEYTCSSNSK
VTVVGMDGGVQPLVETLPEGHVVGKSVRMLNNLDGMFAAGESDIVTRGEYVTNNQKGMRIKS
KGNDLDSNAALLRNDGGSFYILATDKNTTEKPDAANGDWNGLRPFSINMADGRVGMNHGLNIT
GGGLNVTGGNTNLGNITSRVVSSARAGSGWGDNSDAMKSKITFMADHGDLSNSGSYYPIVGA
YSNYGSAGYRQTFEFGWVGSGSTANWREGIIRIRGDNANGQQARWRFTMDGILGCPGKVEM
PETSAFGINTTNGFGGNSIVIGDSDTGFRQVGDGLLEVWTNASRRMRFQGGDTYSDMNINAPN
WIRSDIRLKSNFKPIENALDKVEQLDGLIYDKADYIGGEVVHTEAGVIAQSLEKVLPEAVREVDD
IKGNKVLTVSTQAQVALLIEAVKTLSAKVKELEAKLN
WW170
(SEQ ID NO: 128)
MADLSRIQFKRTSTKGRRPDASTMNPGELAINLADQYLLTKNDSGAIINLSCPPVYDRDVTMAG
KVKGNNYILSKTANYLEDQTARDLNYFGAFRTNGQDGLLDLTLNVPHSAGVNHGRGFTFRYAT
GGSRVETYGYNAQGQKAFSYKMYHEGDKPTPSELNVYSKQEVDRMFVKTVKLATVPVDIVDG
YFKLATAMIPQNGRSVFFRIHGGNGYNVTAYDQVDIVEIVIRSGNNRPKGVNVIAYRRNTNKAF
DVLAVNTSGDNYDIYVKYQRYTDNVIVEFGKSVDVDLVVHDVPDFVVDRPVGDNVIGGRAVTLF
NTENKRGVLSFDDNTQNSYDIVHLSNDRGTGRKYIRKFRSNYNEMIWHETVQGSTYRLATGST
DAQEILSVESSSSIAGTHKGNILSGRMMLGGGSNVITLRRPAGQSNHIAFQDNRTGSITRQGWI
GYGNADTNVFEWYSDVGGTSIRHHIDGQIELATGNTKRVYTNAQFISMNSDAYRMIFGNYGAF
WRNDGTKVYLLSTAEDDKFGGWNGNRPFIYDLTNGKVTLGGDGNEGALVLERDSRAARFAGD
VYVEKGFLHFSSGRQGASGFMKINHLGDIASGRHNILQIEDPTGIHFSTERNDETGNITARFKGF
VRVEAGEIAFDANRGSQSQFTLHTWGNEQRKQVFECKDATGYHWYTERTQGGTGNVLFSMA
GSLNVTSNITTTGADITFKRAGNKHIWFRDPDGLELGLMYCDDAGAIRFRGQKQAQAWKFADK
MIQLESGTVSGGGNGLIRGEVAGGSWSSWRDRAAGLMVGCPQSTNSAHNVWKATHWGKYHI
AAMGIHVPDGTIGNALARLHVHDTNFDFSASGDMTAGRNGSFNDVYIRSDARLKINKEEYKENA
TDKINRLTVYTYDKVKSLTDRTVIAHEVGIIAQDLEKELPEAVTTSKVGDPDKPEEILTISNSAVNA
LLIKAFQEMSEELKAVKAELAELKKN
WW202
(SEQ ID NO: 129)
MADLNRIQFKRTSTAGRKPDAGTMNPGELAINLADQYLLTKNDDGQIVNLSCPPVYDKGFDVR
GRVVVDDLVWSNTANYFDDPTARNLDKFGAFRTNDMDGHLAFALHIPHPSGINHARGFDFTYG
SNVVPTVKTYGYNADGVLAYSYRMYHEGDKPSPSELNVYSKQEVDRMFQKTINFGVETGWFK
IATAFIPQNDGRSLKIRLVGGNGWNVGQTGQCNIIELVIRTSNGSPKGINFVAYHHVSGYENQFC
AINTGDDTYDIYAYYYEFTNMVMAEYQASSDVNLTVFDRPEYVGEKPVAEHIFDAYTIHSFNSFS
NRGTLNFAGNHQGQYDIEHMNEQPTNAKKMLRRFRSSASATIWHETVDDQNYRLATGGTDSV
QQLLLSSGTGLHIRRLTIDGGLGSGSNAGIDIRRGPNESSHFNFMDYRTGQDVRNGWFGFGDL
TTKDFIVWVNDNGQNSINLIENGELHITGGRGQKIVMNSEVALSENARLAVKGGNYGLILRNDGT
GFHILTTDLKDSFGSWNNRRPFSYNFADGGLYLGGTETARCLHLGIDGSTRLEDNLFFKAGSR
QSMDYMELVHWGASNTGRNNVLSLRDSKGFLAEFERVGGTDGVKTRFFGETFTDGTLYLNQ
MNNSSERFSINNWGNSEVGRAAVMEVGDSKGYHFYAERRTDDTVLFDVSGALTVHGPNGITV
KNSTGARHIWFRDDSDTEKAVIWATDDGMLHIRNNHEGSFAHHFQGAMIKLEGRVPYGAAKGL
IRGEVDGGAYVAWRDRPAGLLVDCQKSIDSAHAVWKAVDWGRQYIAAMDVHCPGDGNNTAA
AVLHVQAADYQFHASGEFHASGNGNFNDVYIRSDRRLKDNIEDYTGNALSLIGKLKVKTYDKVK
SLKDREIIGHEIGIIAQDLQEILPEAVKSSKVGNLDNPDDVLTISNSAVNALLIKAIQEMSEEIKELK
TPFFTKIARKISKYFKF

Chimeras SEQUENCES (underlined are the sites used in the fusions shown above):
In italics: Lambda N-terminal part and Underlined: T4-like DTF part
WW13 13.0 (FIG. 8)
(SEQ ID NO: 130)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNRKAPLDSPALTGTPTAPTALRGTNNTQIANTAFVLAAIADVIDASPDALNTL
NELAAALGNDPDFATTMTNALAGKQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGR
DILAKNSVADVLEYLGAGENS IIQLED SQGAHFSTERTLATGAIKTRFFGETFTDGTLYLNQMN
NSSERFSINNWGNSEVGRPAVLEVGDSKGYHFYTERGTDNSLNFDVAGNFTVHGPSGITIKTS
TGARHIWFRDDSDAEKAVIWATDEGILHIRNNYGGSFSHHFQGAMILAGERVPYNSEYALIRG
NISGGAWVDWRGRPAGLLVDCQDSRNQAYNIWKATHWGDQHLAAMGVHAGGGNPQVVLH
VGGNDYAFASNGDFTAGAAVYCNDVYIRSDRRLKINVKDYEENAVDKVNKLKVKTYDKVKSL
SDREVIGHEIGIIAQDLQEVLPEAVSTSSVGSQDNPEEILTISNSAVNALLIKAIQEMSEEIKELKT
PLFTKIARKISKYFKF
WW13 10.0
(SEQ ID NO: 131)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR VDRAV HTLGEITTNAVNGLRIWNNDYGVIFRRSEGSLHIIPTAFGEGETG
DIGPLRPLSIALDTGKVTIPDLQSSYNTFAANGYIKFVGHGAGAGGYDIQYAQAAPIFQEIDOD
AVSKYYPIVKQKFLNGKSVVVSLGTEIESGTFVIHHLKEDGSQGHASRFNQDGTVNFPDNVLV
GGDINMKGMMTFDAGRLGSRDYFKFNHWGDSNNGRDNIIQLEDSQGAHFSTERTLATGAIKT
RFFGETFTDGTLYLNQMNNSSERFSINNWGNSEVGRPAVLEVGDSKGYHFYTERGTDNSLNF
DVAGNFTVHGPSGITIKTSTGARHIWFRDDSDAEKAVIWATDEGILHIRNNYGGSFSHHFQGA
MILAGERVPYNSEYALIRGNISGGAWVDWRGRPAGLLVDCQDSRNQAYNIWKATHWGDQHL
AAMGVHAGGGNPQVVLHVGGNDYAFASNGDFTAGAAVYCNDVYIRSDRRLKINVKDYEENA
VDKVNKLKVKTYDKVKSLSDREVIGHEIGIIAQDLQEVLPEAVSTSSVGSQDNPEEILTISNSAV
NALLIKAIQEMSEEIKELKTPLFTKIARKISKYFKF
WW13-G8 (FIG. 10)
(SEQ ID NO: 132)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR GNIIDL GFAKGGSIDGNVIHIGNYNQTGDYTLNGTFTQTGNFNLTGIARV
TRDIIAAGQIMTEGGELITKSSGTAHVRFFDGNSRERGIIYAPANDGLTTQVLNIRVQDYAAGS
ESTYAFSGSGLFTSPEVSAVVKSMSTPQILTDKVITNGKKTGDYDIYSLSNNTPLAESETAINHL
RVMRNAVGAGIFHEVNVNDGITWYSGDGLDTYLWSFNWAGGLKAGHSISVGLPGGSKGYSE
LGTASIALGDNDTGFKWHQDGYFHTVNNGTRTFIYGPAETQSLRKMVMGYSPDGILMTTPPT
ENYALATVVTYHDNNAFGDGQTLLGYYQGGNYHHYFRGKGTTNINTHGGLLVTPGNIDVIGG
SVNIDGRNNNSTLMFKGYTMGQSSVDNMYIAVWGNTFTNPSEGTRKNVMEISDDIGWMHYIQ
RNKDNTVEAVLNGQQTINENIIAKKDIWVDRAVHTLGEITTNAVNGLRIWNNDYGVIFRRSEGS
LHIIPTAFGEGETGDIGPLRPLSIALDTGKVTIPDLQSSYNTFAANGYIKFVGHGAGAGGYDIQY
AQAAPIFQEIDDDAVSKYYPIVKQKFLNGKSVWSLGTEIESGTFVIHHLKEDGSQGHASRFNQ
DGTVNFPDNVLVGGDINMKGMMTFDAGRLGSRDYFKFNHVVGDSNNGRDNIIQLEDSQGAHF
STERTLATGAIKTRFFGETFTDGTLYLNQMNNSSERFSINNWGNSEVGRPAVLEVGDSKGYH
FYTERGTONSLNFDVAGNFTVHGPSGITIKTSTGARHIWFRDDSDAEKAVIWATDEGILHIRNN
YGGSFSHHFQGAMILAGERVPYNSEYALIRGNISGGAWVDWRGRPAGLLVDCQDSRNQAYN
IWKATHWGDQHLAAMGVHAGGGNPQVVLHVGGNDYAFASNGDFTAGAAVYCNDVYIRSDR
RLKINVKDYEENAVDKVNKLKVKTYDKVKSLSDREVIGHEIGIIAQDLQEVLPEAVSTSSVGSQ
DNPEEILTISNSAVNALLIKAIQEMSEEIKELKTPLFTKIARKISKYFKF
WW13 gp38
(SEQ ID NO: 133)
MAVVGVPGVVIGSSAVNETGQRWMSQAAGQLRLGVPCWMSQFAGRSREIIHTLGADHNFNGQ
WFRDRCFEAGSTPIVFNITGDLVSYSKDVPLFFMYGDTPNEYVQLNIHGVTMYGRGGNGGSNS
PGSAGGHCIQNDIGGRLRINNGGAIAGGGGGGGGGRYGRLSFGGGGGRPFGAGGSSSHMSS
GATAGTISAPGAGSVGEGSLWVYTGGSGGNVGAAGGRCNIQGNGTEYDGGAAGYAVIGSAP
TWINVGAIYGPRV
WW13 gp57A
(SEQ ID NO: 134)
MSEQTIEQKLSAEIVTLKSRILDTQDQAARLMEESKILQGTLAEIARAVGITGDTIKVEEIVEAVKN
LTAESADEAKDEE
PP-1 (FIG. 8)
(SEQ ID NO: 135)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNRKAPLDSPALTGTPTAPTALRGTNNTQIANTAFVLAAIADVIDASPDALNTL
NELAAALGNDPDFATTMTNALAGKQPKNATLTALAGLSTAKNKLPYFAENDAASLTELTQVGR
DILAKNSVADVLEYLGAGENS IATRV SKEGDTMTGKLTLSAGNDALVLTAGEGASSHIRSDVG
GTNNWIGKGSGDNGLGFYSYITQGGVYITNNGEIALSPQGQGTFNFNRDRLHINGTQWTAH
QGGGWENQWNQEAPIFIDFGNVGNDSYYPIIKGKSGITNEGYISGVDFGMRRITNTWAQGIIRV
GNQENGSDPQAIYEFHHNGVLYVPNMVKTGARLSAGGGDPVWQGACVVIGDNDTGLVHGG
DGRINMVANGMHIASWSSAYHLHEGLWDTTGALWTEQGRAIISFGHLVQQSDAYSTFVRDVY
VRSDIRVKKDLVKFENASEKLSKINGYTYMQKRGLDEEGNQKWEPNAGLIAQEVQAILPELVE
GDPDGEALLRLNYNGVIGLNTAAINEHTAEIAELKSEIEELKKIVKSLLK
PP-1 gp38
(SEQ ID NO: 136)
MAVTGPWVGSSAVVNTGQNWMVGAAQRLRMGAPFVVMSNMIGRSVEVIHTLGADHNFNGQW
FRDRCFEAGSAPIVFNITGDLVSYSRDVPLFFMYGDTPNEYVQLNIHGVTMYGRGGNGWAAG
AIGASDGGVCIQNDIGGRLRINNGGAIAGGGGGGGGYSQANNWAGKYVCGGGGGRPFGLGG
NNGARWPGGNASLTSPGAGGNTGTRYYAGGGGEVGQPGQYANPGAGYSTPPTSPGAAVAG
SAPTWQNVGAIYGPRV
PP-1 gp57A
(SEQ ID NO: 137)
MSEQTIEQKLSAEIVTLKSRILDTQDQAARLMEESKILQGTLAEIARAVGITGDTIKVEEIVEAVKN
LTAESTDEAKDEE
>WW55 3.0 (FIG. 9)
(SEQ ID NO: 138)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR TPGEL NVYSKQEIDRMFVKNVKMVVPSGGATRGYFKIASAMIPQSGRM
AFLRIYGGNGYNVNSYDQVDFLEIVIRSGNNNPKGVSIAAYRRNSLNVHEVFAINTSGDNYDIY
VNYGRFTDNVIVEFGKTVDVALTVHDVPEFSATKPETGTKFDARVITMFNTENKAGTLMFDNN
NQLTYDIVSLSNGPDDVRNYLRKFRSKAGEMIWHETVQGAVYRLATGTTDSTEVLRVDSNSA
LPGSYKGYVITGKMELHGSGSAMNLHRQTGQAAYMAWWDRRDGKNQRSGYIGHADGTTD
GFVWRNDVGANSFDLESSGQVNLTTGKTKIVYTNGQYYSANSDAFRMIYGNYGAFWRNDGG
KVYLLSTAENDRFGGWNGNRPFIYDLSTGKVTLGGDGNEGALVLERDSRAARFSNSVFLEK
GLLTFSAGGNQSMDSFTINHWGNSNAGRYNVLQFEDTKGTHFTTERNADGGLLAHFRGDLT
TEGKLTWGKGTATSSFNIRAWGNSDSRKQVFECVDESGWHWYTQRPGGPGTSAIEFAINGT
VKPQAIHTGGNILLNGADIEFRRTGNKHLWFRDPNGLELGLIYCDDNGVIRFRGQKQGQDWV
FANKMIQLGTASTVGGSGNGLIRGQVQGGAWAQWRDRAAGILVDCQQSTDSAHNIWKATH
WGKYHIAAMGVHVPSGTIGNAMARLNVNDANFDFSASGDMSAGRNGSFNDVYIRSDARLKI
NKEEYKENATDKVNRLTVYTYDKVKSLTDRTVIAHEVGIIAQDLEKELPEAVTTSKIGDPDKPE
EILTISNSAVNALLIKAFQEMSEELKAVKAELAELKK
>WW55-G8 (FIG. 10)
(SEQ ID NO: 139)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR GAIIN LSCPPVYDRDVTMAGKVKGNNYILSKTANYLEDQTARDLNYFGA
FRTNGLDGLLELTLNVPHSSGVQHGRGFTFQYGHTGSRVETYGYNKEGQKAFSYKMYHEGD
KPTPGELNVYSKQEIDRMFVKNVKMVVPSGGATRGYFKIASAMIPQSGRMAFLRIYGGNGYN
VNSYDQVDFLEIVIRSGNNNPKGVSIAAYRRNSLNVHEVFAINTSGDNYDIYVNYGRFTDNVIVE
FGKTVDVALTVHDVPEFSATKPETGTKFDARVITMFNTENKAGTLMFDNNNQLTYDIVSLSNG
PDDVRNYLRKFRSKAGEMIWHETVQGAVYRLATGTTDSTEVLRVDSNSALPGSYKGYVITGK
MELHGSGSAMNLHRQTGQAAYMAWWDRRDGKNQRSGYIGHADGTTDGFVWRNDVGANS
FDLESSGQVNLTTGKTKIVYTNGQYYSANSDAFRMIYGNYGAFWRNDGGKVYLLSTAENDRF
GGWNGNRPFIYDLSTGKVTLGGDGNEGALVLERDSRAARFSNSVFLEKGLLTFSAGGNQSM
DSFTINHWGNSNAGRYNVLQFEDTKGTHFTTERNADGGLLAHFRGDLTTEGKLTWGKGTAT
SSFNIRAWGNSDSRKQVFECVDESGWHWYTQRPGGPGTSAIEFAINGTVKPQAIHTGGNILL
NGADIEFRRTGNKHLWFRDPNGLELGLIYCDDNGVIRFRGQKQGQDWVFANKMIQLGTASTV
GGSGNGLIRGQVQGGAWAQWRDRAAGILVDCQQSTDSAHNIWKATHWGKYHIAAMGVHVP
SGTIGNAMARLNVNDANFDFSASGDMSAGRNGSFNDVYIRSDARLKINKEEYKENATDKVNR
LTVYTYDKVKSLTDRTVIAHEVGIIAQDLEKELPEAVTTSKIGDPDKPEEILTISNSAVNALLIKA
FQEMSEELKAVKAELAELKKN
>WW55 gp38
(SEQ ID NO: 140)
MAISSGWVGSSAVSETGQRWMSAAMQAVRLGRPAYMSAMVGRSKEIHYSIGASNSYNKDTLI
NWMKAQGSTPVVITITGNIVSQSTGVPCLDFPSSLTNEYVTLIINSGVHVLGRGGNGGSNSAGG
AGGNAINNGIGTRLRINNNGIIGGGGGGGAGARYNPFPQMDMKFGGGGGRPFGAAGAAGGG
AAAASAGTISAPGKGTVSGVHYGGDGGDLGAAGKSSYIKGGTGGTVHSGGAAGKAVTGNAPR
WDKVGTIYGARV
WW55 gp57A
(SEQ ID NO: 141)
MSNQHEQMINVLKVRLFDTQEKAAFLEGQLKDRERVLMELVRILGIQPDENGTVSLDAIVEEVK
ALLPKDEAAEDAEEEVELITEA
WW34 3.0
(SEQ ID NO: 142)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR TPGEL NVYSKQEIDRMFVKNVKMSTPSGEATRGYFKIASAMIPQSGRM
AFLRIYGGNGFNVNSYDQVDFLEIVIRSGNNNPKGVSIAAYRRNSLNVHEVFAINTSGDNYDIY
VNYGRFTDNVIVEFGKTVDVALTVHDVPEFSATKPETGTKFDARVITMFNTENKAGTLMFDNN
NQLTYDIVSLSNGPDDVRNYLRKFRSKAGEMIWHETVQGAVYRLATGTTDSTEVLRVDSNSAI
PGSYKGYVITGKMELHGSGNSMILHRQTAQAAYMSWWDRRDGKNQRSGYIGHADGTSDAIV
WNNDIGQNSAVLETSGQISFRTGATKIVYTNGQYYSANSDAYRMIFGNYGAFWRNDGTKVYL
LSTAENDKYGGWNAYRPFIYDLTSGNVQLGGDGNEDALTLECASRAARFSNDVYIKKGLLTF
DAGRAGSRDYIRFNHWGDSNNARDNVLCIEDSQGRHFSTERAMGTGALKAYFLGDLEVGGK
FTWGKNTATSSFNIRAWGNDSRKQVLECADESGWHWYTQRTGGPDTSAIDFAINGTVRPQAI
HTGGNITINGADIEFKRTGNKHIWFRDPNGLELGLMYCDDAGAIRFRGQKQAQAWKFADKMI
QLESGTVSGGGNGLIRGEVAGGSWASWRDRAAGLMVGCPQSTNSAHNVWKATHWGKYHI
AAMAVHVPDGTITNALARLNVHDANFDFSASGDLSAGRNGSFNDVYIRSDARLKINKEEYKE
NATDKVNRLTVYTYDKVKSLTDRTVIAHEVGIIAQDLEKELPEAVTTSKIGDPDKPEEILTISNS
AVNALLIKAFQEMSEELKAVKAELAELKKN
WW34 gp38
(SEQ ID NO: 143)
MAISSGWVGSSAVSETGQRWMSAAMQAVRLGRPAYMSAMVGRSKEIHYSIGASNSYNKDTLI
NWMKAQGSTPVVITITGNIVSQSTGVPCLDFPSSLTNEYVTLIINPGVHVWGRGGNGGNNSAG
GAGGNAINNGIGTRLRITNNGAICGGGGGGGGGYYSPFSQMRLTFGGGGGRPFGAAGGSAN
MEQGATAGTISAPGKGSVNGVYNGGNGGDAGGAGGKCNIRGQGSEYNGGAAGKAVTGNAP
RWDKVGTIYGARV
WW34 gp57A
(SEQ ID NO: 144)
MSNQHEQMINVLKVRLFDTQEKAAFLEGQLKDRERVLMELVRILGIQPDENGTVSLDAIVEEVK
ALLPKDEAAEDAEEEVELITEA
WW14-G8
(SEQ ID NO: 145)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR NQIID LGFAKGGQVDGDVTINGTLNLNGPEIVASGGYIEFNYRTTGSGS
WAGQHAAKAPIFVDLSAALSTSEYNPLFKQRYKDGTFSAGTLVTEGSFKFHYINEAGDSKYW
TFNRNGNFQVDTGSLFVSGGNISASGNINSASGFVSAPQINTKNIILDTKAFGQYDSQSLVNYV
YPGTGETNGVNYLRKVRAKSGGTMWHELCTAQLGQADEMSWWTGNTPQSKQYGVRNDGR
LIGRNSLALGTMTTDFPSSDYGNTGAMGDKYLVLGDTATGLKYIKQGNFDLVGGGYSVASITT
DGFRGTSKTLFGRSNDQGLTWLLPGQNSAMVSIRTEIDGNNSGDGQTHLGYNSNGKLYHYF
RGTGRVAISMAEGMIIEPGILNIKTGVNELNLRADGTVSTTQRLMVNNGLVLNANNNTSALALT
APTGVDGTKTINWDAGTRNGQNKNTVTMKAWGNSFNAGGGNRETVFEVSDSQGYYFYGQR
TNPASGETVGPINFKFNGSVETGHFSSLGNISASGTGSFGGNVTMTNGLFVQGGASINGQVK
MGGTADALRIWNAEYGMIFRRSETGSSASFHLIPTLQNAGENGGISDLRPLSINLASGTVIMG
NKSTGGPLFTVDNVSKFVQTDCRLRVNMDSDGIVLNASSQAASNFIQGRKADVTKVVYLGIGD
GGNVVRMHNYTYSHGIALNSDTVDITKPLKIGSDIRIGTDGNIIGSATLDNFKNLNTTLDHKVNM
GGWSGGATTGWYKFATVEIPQATGTASFKIFGGSGFNFKSYGQASIAEIILRTGNNNPKGLNA
TLWNRTSEAISQIASVNTSEDIYDIYVYLGGYSNSLVVEYTCSSNSKVTVVGMDGGVQPLVETL
PEGHVVGKSVRMLNNLDGMFAAGESDIVTRGEYVTNNQKGMRIKSKGNDLDSNAALLRNDG
GSFYILATDKNTTEKPDAANGDWNGLRPFSINMADGRVGMNHGLNITGGGLNVTGGNTNLG
NITSRVVSSARAGSGWGDNSDAMKSKITFMADHGDLSNSGSYYPIVGAYSNYGSAGYRQTF
EFGWVGSGSTANWREGIIRIRGDNANGQQARWRFTMDGILGCPGKVEMPETSAFGINTTNGF
GGNSIVIGDSDTGFRQVGDGLLEVWTNASRRMRFQGGDTYSDMNINAPNVYIRSDIRLKSNFK
PIENALDKVEQLDGLIYDKADYIGGEVVHTEAGVIAQSLEKVLPEAVREVDDIKGNKVLTVSTQ
AQVALLIEAVKTLSAKVKELEAKLN
WW14 gp38
(SEQ ID NO: 146)
MAIVGVPGWIGQSAVDETGQRWMDAAMRDVRVAVPGWMGSMAGQSKEIYLSIGANNSYDRN
SLINWMRAQGGAPVVITITGNLVSNSTGNACLEFPSNLPNAYIQLIINSGVTVYGRGGNGSTNG
SAGGNGGTAIHNAAGTKLRIRNNGAIAGGGGGGGAVSLQNSYPTNGTCGGGGGRPFGVGGKI
GSDAILSGSNASLTAAGTGGATVQYGGGNGGNVGAGGGRGWGKNVYTSAGGSAGAAVTGN
APNWQNVGTIYGSRV
WW14 gp57A
(SEQ ID NO: 147)
MSEQTIEQKLQAEIVALKSRILDTQDVAAQAQQESRILQDALSKIAARLGITGDQIQIEDLIAAVPD
LTAESADEE
WW170-G8
(SEQ ID NO: 148)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR GAIIN LSCPPVYDRDVTMAGKVKGNNYILSKTANYLEDQTARDLNYFGA
FRTNGQDGLLDLTLNVPHSAGVNHGRGFTFRYATGGSRVETYGYNAQGQKAFSYKMYHEG
DKPTPSELNVYSKQEVDRMFVKTVKLATVPVDIVDGYFKLATAMIPQNGRSVFFRIHGGNGYN
VTAYDQVDIVEIVIRSGNNRPKGVNVIAYRRNTNKAFDVLAVNTSGDNYDIYVKYQRYTDNVIV
EFGKSVDVDLVVHDVPDFVVDRPVGDNVIGGRAVTLFNTENKRGVLSFDDNTQNSYDIVHLS
NDRGTGRKYIRKFRSNYNEMIWHETVQGSTYRLATGSTDAQEILSVESSSSIAGTHKGNILSG
RMMLGGGSNVITLRRPAGQSNHIAFQDNRTGSITRQGWIGYGNADTNVFEWYSDVGGTSIRH
HIDGQIELATGNTKRVYTNAQFISMNSDAYRMIFGNYGAFWRNDGTKVYLLSTAEDDKFGGW
NGNRPFIYDLTNGKVTLGGDGNEGALVLERDSRAARFAGDVYVEKGFLHFSSGRQGASGFM
KINHLGDIASGRHNILQIEDPTGIHFSTERNDETGNITARFKGFVRVEAGEIAFDANRGSQSQFT
LHTWGNEQRKQVFECKDATGYHWYTERTQGGTGNVLFSMAGSLNVTSNITTTGADITFKRA
GNKHIWFRDPDGLELGLMYCDDAGAIRFRGQKQAQAWKFADKMIQLESGTVSGGGNGLIRG
EVAGGSWSSWRDRAAGLMVGCPQSTNSAHNVWKATHWGKYHIAAMGIHVPDGTIGNALAR
LHVHDTNFDFSASGDMTAGRNGSFNDVYIRSDARLKINKEEYKENATDKINRLTVYTYDKVKS
LTDRTVIAHEVGIIAQDLEKELPEAVTTSKVGDPDKPEEILTISNSAVNALLIKAFQEMSEELKA
VKAELAELKKN
WW170 gp38
(SEQ ID NO: 149)
MAISSGWVGSSAVSETGQRVVMSAAMQAVRLGRPAYMSAMVGRSKEIHYSIGASNSYNKDTLI
NWMKAQGSTPVVITITGNIVSQSTGVPCLDFPSSLTNEYVTLIINPGVHVWGRGGNGGNNSAG
GAGGNAINNGIGTRLRITNNGAICGGGGGGGGGYYSPFSQMRLTFGGGGGRPFGAAGGSAN
MEQGATAGTISAPGKGSVNGVYNGGNGGDAGGAGGKCNIRGQGSEYNGGAAGKAVTGNAP
RVVDKVGTIYGARV
WW170 gp57A
(SEQ ID NO: 150)
MSNQHEQMINVLKVRLFDTQEKAAFLEGQLKDRERVLMELVRILGIQPDENGTVSLDAIVEEVK
ALLPKDEAAEDAKEEVELITEA
WW202-G8
(SEQ ID NO: 151)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSVILQ
VDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVVAQSTAD
AKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKATEAEKSAA
AAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAVASKEAAKSSET
NASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKTAAAGSASTASTKAT
EAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTRKGIVQLSSATNSTSETLAA
TPKAVKVVMDETNR GQIVN LSCPPVYDKGFDVRGRVVVDDLVWSNTANYFDDPTARNLDKF
GAFRTNDMDGHLAFALHIPHPSGINHARGFDFTYGSNVVPTVKTYGYNADGVLAYSYRMYHE
GDKPSPSELNVYSKQEVDRMFQKTINFGVETGWFKIATAFIPQNDGRSLKIRLVGGNGWNVG
QTGQCNIIELVIRTSNGSPKGINFVAYHHVSGYENQFCAINTGDDTYDIYAYYYEFTNMVMAEY
QASSDVNLTVFDRPEYVGEKPVAEHIFDAYTIHSFNSFSNRGTLNFAGNHQGQYDIEHMNEQP
TNAKKMLRRFRSSASATIWHETVDDQNYRLATGGTDSVQQLLLSSGTGLHIRRLTIDGGLGS
GSNAGIDIRRGPNESSHFNFMDYRTGQDVRNGWFGFGDLTTKDFIWWNDNGQNSINLIENGE
LHITGGRGQKIVMNSEVALSENARLAVKGGNYGLILRNDGTGFHILTTDLKDSFGSWNNRRPF
SYNFADGGLYLGGTETARCLHLGIDGSTRLEDNLFFKAGSRQSMDYMELVHWGASNTGRNN
VLSLRDSKGFLAEFERVGGTDGVKTRFFGETFTDGTLYLNQMNNSSERFSINNWGNSEVGRA
AVMEVGDSKGYHFYAERRTDDTVLFDVSGALTVHGPNGITVKNSTGARHIWFRDDSDTEKAV
IWATDDGMLHIRNNHEGSFAHHFQGAMIKLEGRVPYGAAKGLIRGEVDGGAYVAWRDRPAG
LLVDCQKSIDSAHAVWKAVDWGRQYIAAMDVHCPGDGNNTAAAVLHVQAADYQFHASGEF
HASGNGNFNDVYIRSDRRLKDNIEDYTGNALSLIGKLKVKTYDKVKSLKDREIIGHEIGIIAQDL
QEILPEAVKSSKVGNLDNPDDVLTISNSAVNALLIKAIQEMSEEIKELKTPFFTKIARKISKYFKF
WW202 gp38
(SEQ ID NO: 152)
MAVVGVPGWIGSSAANETGQRWMSQAAGQLRLGVPCWMSQFSGRSREIIHTLGADHNFNGQ
WFRDRCFEAGSTPIVFNITGDLVSYSKDVPLFFMYGDTPNEYVQLNIHGVTMYGRGGNGGSNS
PGSAGGHCIQNDIGGRLRINNGGAIAGGGGGGGGGYYSPFSQMRLTFGGGGGRPFGAPGGS
IDMQSGATAGTLYAPGSGSVNGIYNGGSGGEVGAAGGRCNIRGQGYEYNGGDAGYAVIGSSP
TVVQNRGAIYGPAV
WW202 gp57A
(SEQ ID NO: 153)
MSNQHEQMINVLKVRLFDTQEKAAFLEGQLKDRERVLMELVRVLGIQPDENGTVSLDAIVEEVK
ALLPKDEAAEDAKEEVELITEA

Chimeras nucleotide sequence
WW13 13.0
(SEQ ID NO: 154)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGATCATCCAGTTAGAAGATAGTCAAGGCGCCCATTTTTCCACTGAA
CGTACTTTAGCGACAGGTGCAATTAAAACTCGTTTCTTTGGCGAAACATTTACTGAT
GGTACATTATACCTAAATCAGATGAATAATAGTTCTGAACGATTCTCTATTAATAAT
TGGGGAAATTCAGAAGTTGGTCGCCCGGCAGTGTTGGAAGTCGGTGATTCCAAAGG
TTATCACTTCTATACGGAACGCGGGACAGATAACAGTTTGAATTTTGATGTTGCTGG
CAATTTTACTGTGCATGGACCTTCCGGGATTACTATCAAAACCTCTACTGGTGCTCGC
CATATCTGGTTTAGAGATGATAGCGATGCAGAAAAGGCTGTTATCTGGGCTACAGAT
GAGGGTATTTTACATATACGAAATAATTATGGGGGTTCATTTAGTCATCACTTCCAG
GGTGCAATGATTCTAGCGGGAGAGCGTGTTCCATATAATAGTGAATACGCTCTTATC
CGTGGTAATATTTCCGGTGGTGCATGGGTAGACTGGCGAGGTCGTCCGGCTGGATTG
TTGGTAGACTGTCAGGACTCACGAAATCAAGCATATAACATTTGGAAAGCTACTCAT
TGGGGCGACCAGCACCTTGCGGCGATGGGTGTTCATGCTGGCGGTGGTAATCCTCAG
GTTGTATTGCATGTGGGTGGGAATGATTATGCATTTGCATCTAACGGTGATTTTACTG
CTGGTGCTGCTGTATATTGTAACGACGTTTATATTCGTTCTGACCGTCGTCTGAAAAT
TAATGTTAAAGACTACGAAGAGAATGCGGTGGATAAGGTAAATAAACTCAAAGTTA
AAACCTATGATAAAGTTAAATCTCTTTCTGACCGCGAAGTTATCGGCCATGAGATTG
GTATTATCGCACAGGATTTGCAAGAAGTATTACCGGAAGCTGTTAGCACTTCTAGTG
TCGGATCTCAGGATAACCCAGAAGAAATTTTAACAATTTCTAACTCTGCTGTGAACG
CGCTTTTAATTAAGGCTATTCAGGAAATGAGTGAAGAAATTAAAGAATTGAAAACG
CCTCTCTTTACTAAAATTGCTCGCAAAATTAGTAAATATTTTAAATTCTAA
WW13 10.0
(SEQ ID NO: 155)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTGTTGACCGAGCAGTTCACACCCTTGGCGAAATCACTACAAATGCTGTTAATGGT
CTTCGTATTTGGAATAATGATTATGGAGTCATTTTTAGACGTTCAGAAGGAAGTCTT
CATATTATTCCTACCGCATTTGGTGAAGGAGAAACCGGTGATATTGGACCTTTACGT
CCTCTCAGTATAGCTTTAGATACCGGTAAAGTTACTATTCCGGATTTACAATCAAGTT
ACAATACGTTCGCTGCTAACGGTTATATTAAATTTGTTGGTCATGGAGCGGGGGCCG
GCGGTTATGACATTCAATATGCTCAAGCGGCTCCTATTTTCCAGGAAATCGATGATG
ATGCTGTAAGCAAATATTATCCTATTGTTAAACAGAAGTTTTTAAACGGTAAATCCG
TTTGGTCTTTAGGTACCGAAATTGAATCAGGTACATTCGTTATTCATCATCTGAAAG
AAGATGGTTCACAAGGCCATGCGTCTCGTTTTAATCAAGACGGTACTGTTAACTTCC
CGGATAACGTTCTGGTCGGCGGTGATATTAACATGAAAGGCATGATGACTTTTGACG
CCGGACGTTTAGGATCACGAGATTATTTTAAATTTAACCATTGGGGTGATAGTAATA
ATGGTCGTGATAACATCATCCAGTTAGAAGATAGTCAAGGCGCCCATTTTTCCACTG
AACGTACTTTAGCGACAGGTGCAATTAAAACTCGTTTCTTTGGCGAAACATTTACTG
ATGGTACATTATACCTAAATCAGATGAATAATAGTTCTGAACGATTCTCTATTAATA
ATTGGGGAAATTCAGAAGTTGGTCGCCCGGCAGTGTTGGAAGTCGGTGATTCCAAA
GGTTATCACTTCTATACGGAACGCGGGACAGATAACAGTTTGAATTTTGATGTTGCT
GGCAATTTTACTGTGCATGGACCTTCCGGGATTACTATCAAAACCTCTACTGGTGCT
CGCCATATCTGGTTTAGAGATGATAGCGATGCAGAAAAGGCTGTTATCTGGGCTACA
GATGAGGGTATTTTACATATACGAAATAATTATGGGGGTTCATTTAGTCATCACTTC
CAGGGTGCAATGATTCTAGCGGGAGAGCGTGTTCCATATAATAGTGAATACGCTCTT
ATCCGTGGTAATATTTCCGGTGGTGCATGGGTAGACTGGCGAGGTCGTCCGGCTGGA
TTGTTGGTAGACTGTCAGGACTCACGAAATCAAGCATATAACATTTGGAAAGCTACT
CATTGGGGCGACCAGCACCTTGCGGCGATGGGTGTTCATGCTGGCGGTGGTAATCCT
CAGGTTGTATTGCATGTGGGTGGGAATGATTATGCATTTGCATCTAACGGTGATTTT
ACTGCTGGTGCTGCTGTATATTGTAACGACGTTTATATTCGTTCTGACCGTCGTCTGA
AAATTAATGTTAAAGACTACGAAGAGAATGCGGTGGATAAGGTAAATAAACTCAAA
GTTAAAACCTATGATAAAGTTAAATCTCTTTCTGACCGCGAAGTTATCGGCCATGAG
ATTGGTATTATCGCACAGGATTTGCAAGAAGTATTACCGGAAGCTGTTAGCACTTCT
AGTGTCGGATCTCAGGATAACCCAGAAGAAATTTTAACAATTTCTAACTCTGCTGTG
AACGCGCTTTTAATTAAGGCTATTCAGGAAATGAGTGAAGAAATTAAAGAATTGAA
AACGCCTCTCTTTACTAAAATTGCTCGCAAAATTAGTAAATATTTTAAATTCTAA
WW13-G8
(SEQ ID NO: 156)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTGGAAATATTATTGATCTGGGTTTTGCTAAAGGCGGTAGTATTGACGGAAATGTT
ATTCATATAGGAAATTATAATCAAACTGGTGATTATACTTTAAATGGCACCTTCACT
CAGACAGGTAATTTTAATTTAACTGGTATTGCTCGAGTAACTCGCGATATTATTGCC
GCCGGGCAAATTATGACTGAGGGCGGAGAACTTATTACAAAAAGTTCAGGTACAGC
ACATGTTCGTTTTTTCGATGGCAATAGCCGCGAACGTGGAATCATTTATGCCCCGGC
CAATGATGGTTTAACTACGCAAGTTCTTAATATCAGGGTTCAAGACTACGCCGCTGG
TAGCGAAAGCACTTATGCATTTTCAGGCAGTGGCCTATTTACTTCACCTGAAGTATC
GGCATGGAAATCTATGTCAACTCCTCAGATTTTGACCGATAAAGTTATTACAAATGG
GAAGAAGACAGGCGATTATGATATCTATTCATTATCAAATAACACTCCATTGGCAGA
AAGCGAAACGGCTATTAACCACCTCCGTGTTATGCGAAATGCTGTAGGAGCAGGTA
TTTTCCACGAAGTTAATGTTAATGACGGAATAACCTGGTATTCCGGAGATGGCTTAG
ACACTTATCTTTGGTCGTTTAACTGGGCCGGTGGATTGAAAGCTGGTCATTCTATTTC
TGTAGGTCTTCCGGGTGGCTCTAAAGGATATTCTGAATTAGGAACGGCCTCAATTGC
TCTTGGTGATAATGACACCGGATTTAAATGGCATCAGGACGGATATTTTCATACAGT
AAACAATGGAACAAGAACTTTCATCTACGGCCCTGCGGAAACACAAAGCCTTAGAA 
AAATGGTTATGGGTTATTCTCCGGACGGGATTCTTATGACAACGCCACCGACAGAAA 
ACTATGCTCTTGCTACTGTAGTGACATACCACGATAATAACGCGTTTGGAGATGGTC 
AAACTCTTTTAGGATATTATCAAGGCGGTAACTATCATCACTATTTCCGCGGTAAGG 
GTACTACAAACATTAATACTCATGGCGGTTTGTTAGTTACTCCAGGCAATATTGACG 
TTATTGGTGGTTCTGTTAATATCGATGGTAGAAATAATAATTCAACTTTAATGTTTAA 
AGGCTATACCATGGGTCAAAGCTCCGTTGATAACATGTATATAGCTGTTTGGGGAAA 
TACATTTACTAATCCTAGTGAAGGCACCCGTAAAAATGTCATGGAAATTTCTGATGA 
TATTGGATGGATGCATTATATTCAACGAAATAAAGATAATACAGTTGAAGCCGTATT 
AAATGGTCAACAGACAATTAACGAAAATATTATTGCGAAAAAGGATATTTGGGTTG 
ACCGAGCAGTTCACACCCTTGGCGAAATCACTACAAATGCTGTTAATGGTCTTCGTA 
TTTGGAATAATGATTATGGAGTCATTTTTAGACGTTCAGAAGGAAGTCTTCATATTA 
TTCCTACCGCATTTGGTGAAGGAGAAACCGGTGATATTGGACCTTTACGTCCTCTCA 
GTATAGCTTTAGATACCGGTAAAGTTACTATTCCGGATTTACAATCAAGTTACAATA 
CGTTCGCTGCTAACGGTTATATTAAATTTGTTGGTCATGGAGCGGGGGCCGGCGGTT 
ATGACATTCAATATGCTCAAGCGGCTCCTATTTTCCAGGAAATCGATGATGATGCTG 
TAAGCAAATATTATCCTATTGTTAAACAGAAGTTTTTAAACGGTAAATCCGTTTGGT 
CTTTAGGTACCGAAATTGAATCAGGTACATTCGTTATTCATCATCTGAAAGAAGATG 
GTTCACAAGGCCATGCGTCTCGTTTTAATCAAGACGGTACTGTTAACTTCCCGGATA 
ACGTTCTGGTCGGCGGTGATATTAACATGAAAGGCATGATGACTTTTGACGCCGGAC 
GTTTAGGATCACGAGATTATTTTAAATTTAACCATTGGGGTGATAGTAATAATGGTC 
GTGATAACATCATCCAGTTAGAAGATAGTCAAGGCGCCCATTTTTCCACTGAACGTA 
CTTTAGCGACAGGTGCAATTAAAACTCGTTTCTTTGGCGAAACATTTACTGATGGTA 
CATTATACCTAAATCAGATGAATAATAGTTCTGAACGATTCTCTATTAATAATTGGG 
GAAATTCAGAAGTTGGTCGCCCGGCAGTGTTGGAAGTCGGTGATTCCAAAGGTTATC 
ACTTCTATACGGAACGCGGGACAGATAACAGTTTGAATTTTGATGTTGCTGGCAATT 
TTACTGTGCATGGACCTTCCGGGATTACTATCAAAACCTCTACTGGTGCTCGCCATAT 
CTGGTTTAGAGATGATAGCGATGCAGAAAAGGCTGTTATCTGGGCTACAGATGAGG 
GTATTTTACATATACGAAATAATTATGGGGGTTCATTTAGTCATCACTTCCAGGGTG 
CAATGATTCTAGCGGGAGAGCGTGTTCCATATAATAGTGAATACGCTCTTATCCGTG 
GTAATATTTCCGGTGGTGCATGGGTAGACTGGCGAGGTCGTCCGGCTGGATTGTTGG 
TAGACTGTCAGGACTCACGAAATCAAGCATATAACATTTGGAAAGCTACTCATTGGG 
GCGACCAGCACCTTGCGGCGATGGGTGTTCATGCTGGCGGTGGTAATCCTCAGGTTG 
TATTGCATGTGGGTGGGAATGATTATGCATTTGCATCTAACGGTGATTTTACTGCTG 
GTGCTGCTGTATATTGTAACGACGTTTATATTCGTTCTGACCGTCGTCTGAAAATTAA 
TGTTAAAGACTACGAAGAGAATGCGGTGGATAAGGTAAATAAACTCAAAGTTAAAA 
CCTATGATAAAGTTAAATCTCTTTCTGACCGCGAAGTTATCGGCCATGAGATTGGTA 
TTATCGCACAGGATTTGCAAGAAGTATTACCGGAAGCTGTTAGCACTTCTAGTGTCG 
GATCTCAGGATAACCCAGAAGAAATTTTAACAATTTCTAACTCTGCTGTGAACGCGC 
TTTTAATTAAGGCTATTCAGGAAATGAGTGAAGAAATTAAAGAATTGAAAACGCCT 
CTCTTTACTAAAATTGCTCGCAAAATTAGTAAATATTTTAAATTCTAA 
WW13 GP38
(SEQ ID NO: 157)
ATGGCAGTAGTTGGAGTTCCTGGCTGGATTGGAAGTTCAGCCGTAAATGAAACGGG 
TCAGCGCTGGATGAGTCAAGCAGCTGGTCAATTAAGATTGGGTGTTCCTTGCTGGAT 
GAGTCAATTTGCAGGTCGCTCAAGAGAAATTATTCATACACTTGGAGCAGACCATAA 
CTTCAATGGTCAATGGTTCCGAGATAGATGTTTTGAGGCAGGTAGTACACCTATAGT 
GTTTAATATCACTGGAGATTTAGTATCATATTCTAAAGATGTTCCTTTATTCTTCATG 
TACGGAGATACACCGAATGAATATGTTCAACTGAATATACACGGCGTAACGATGTA 
TGGACGTGGCGGTAATGGCGGTAGCAATAGTCCTGGTTCAGCTGGAGGTCATTGTAT 
TCAAAACGATATTGGTGGGAGACTAAGAATTAATAACGGTGGAGCTATTGCCGGCG 
GCGGCGGTGGCGGCGGTGGCGGTAGATATGGCAGACTATCATTTGGTGGTGGCGGT 
GGTCGCCCATTCGGTGCTGGCGGGTCTTCCTCTCATATGAGTTCCGGTGCAACTGCT 
GGCACCATTTCCGCTCCGGGTGCAGGATCTGTCGGTGAGGGATCTCTTTGGGTATAT 
ACAGGCGGTTCGGGTGGTAATGTCGGTGCTGCTGGAGGAAGATGTAATATTCAAGG 
TAACGGTACAGAATATGATGGCGGTGCTGCTGGTTATGCTGTTATAGGGTCTGCTCC 
AACTTGGATAAATGTTGGAGCAATATATGGTCCAAGAGTATAA 
WW13 GP57A
(SEQ ID NO: 158)
ATGTCTGAACAAACTATTGAACAAAAACTGTCTGCTGAAATCGTAACTCTGAAGTCT 
CGTATCCTTGATACGCAGGACCAAGCGGCTCGTCTGATGGAAGAATCCAAAATTCTG 
CAAGGAACTTTGGCTGAAATTGCTCGTGCAGTAGGTATCACTGGCGATACTATCAAA 
GTTGAAGAAATCGTTGAAGCTGTCAAGAATCTTACTGCTGAATCTGCAGATGAAGCA 
AAAGATGAAGAATGA 
PP-1
(SEQ ID NO: 159)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACAGCACCAACCGC
GCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGGCCGCGA
TTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCCG
CAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTA
AACAACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAAT
AAATTACCGTATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTT
GGCAGGGATATTCTGGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCC
GGTGAGAATTCGATCGCTACCCGCGTGTCCAAAGAAGGTGACACTATGACTGGTAA
GCTGACTCTGTCTGCGGGTAACGATGCGCTGGTGCTGACTGCGGGCGAGGGCGCGTC
CTCGCACATTCGCTCTGACGTGGGCGGGACGAACAACTGGTATATCGGTAAAGGCA
GTGGGGATAACGGTTTAGGCTTCTACTCATACATCACTCAGGGCGGGGTGTATATTA
CCAACAACGGGGAAATCGCTTTAAGCCCGCAGGGTCAGGGTACGTTTAACTTCAAC
CGTGATCGTCTGCACATCAACGGCACGCAATGGACGGCACATCAAGGCGGTGGCTG
GGAAAACCAGTGGAATCAGGAAGCGCCGATTTTTATTGATTTCGGCAACGTGGGCA
ATGATAGCTACTACCCGATTATCAAAGGTAAGTCCGGCATTACCAACGAAGGTTATA
TTTCTGGCGTGGACTTCGGTATGCGTCGGATTACTAACACGTGGGCGCAGGGTATTA
TCCGCGTAGGCAATCAGGAAAACGGTAGCGATCCGCAGGCCATCTACGAGTTCCAT
CATAATGGCGTACTGTACGTTCCTAATATGGTAAAAACGGGTGCGCGTCTGAGCGCA
GGTGGGGGGGATCCGGTATGGCAGGGTGCATGTGTTGTTATCGGTGACAATGACAC
GGGCTTAGTGCATGGTGGCGATGGTCGCATCAATATGGTTGCAAACGGTATGCACAT
TGCGTCTTGGAGTTCCGCGTATCATTTACATGAGGGTTTATGGGATACTACGGGCGC
GTTATGGACGGAGCAAGGGCGTGCAATTATCAGCTTCGGTCATCTGGTACAACAAA
GCGATGCCTATTCCACCTTTGTCCGTGATGTATACGTTCGTTCGGATATTCGCGTTAA
AAAAGATCTGGTGAAATTCGAAAACGCTAGCGAAAAACTGTCCAAAATCAACGGTT
ATACTTATATGCAGAAACGCGGGTTAGACGAAGAAGGTAATCAGAAATGGGAGCCT
AACGCCGGATTAATCGCGCAGGAAGTGCAGGCGATTCTGCCGGAACTGGTAGAAGG
CGATCCGGACGGTGAAGCATTATTACGTCTGAACTACAATGGCGTGATCGGCCTGAA
TACTGCGGCGATTAATGAACATACGGCAGAGATCGCGGAGCTGAAAAGCGAGATTG
AAGAACTGAAAAAAATTGTCAAAAGCCTGTTAAAGTAA
PP-1 GP38
(SEQ ID NO: 160)
ATGGCAGTAACAGGACCGTGGGTAGGATCGTCTGCAGTAGTTAATACAGGACAAAA
TTGGATGGTCGGCGCGGCCCAACGATTAAGAATGGGTGCTCCGTTCTGGATGAGCA
ACATGATTGGGCGCTCTGTTGAAGTGATTCATACGTTAGGCGCAGATCATAATTTTA
ATGGTCAATGGTTTCGTGACCGTTGCTTTGAGGCGGGCAGTGCGCCGATCGTGTTTA
ACATCACTGGCGATTTAGTTTCTTACTCCCGTGACGTTCCGCTGTTTTTCATGTATGG
TGACACGCCGAACGAGTATGTACAATTAAACATTCACGGTGTCACGATGTACGGGC
GCGGGGGCAACGGTTGGGCGGCGGGTGCAATCGGTGCGAGCGATGGCGGGGTGTGC
ATCCAGAATGATATTGGAGGCCGACTGCGTATCAACAATGGTGGGGCAATCGCGGG
CGGTGGCGGTGGTGGGGGTGGTTATTCTCAGGCTAACAATTGGGCAGGTAAGTACG
TTTGCGGTGGCGGTGGCGGTCGTCCGTTCGGCTTAGGTGGCAACAACGGTGCGCGTT
GGCCTGGGGGCAACGCTAGCCTGACCTCGCCGGGCGCAGGTGGGAACACTGGCACG
CGTTATTACGCTGGCGGGGGAGGTGAGGTTGGTCAGCCGGGTCAGTATGCAAACCC
CGGCGCGGGTTACTCCACCCCACCAACGTCGCCGGGCGCGGCAGTTGCAGGTAGTG
CGCCAACTTGGCAAAACGTGGGCGCTATTTATGGCCCGCGTGTTTAA
PP-1 GP57A
(SEQ ID NO: 161)
ATGAGTGAACAGACCATCGAACAAAAATTAAGCGCGGAAATCGTGACTCTGAAAAG
TCGCATTCTGGATACTCAGGACCAGGCAGCACGTCTGATGGAAGAGTCTAAAATCTT
GCAGGGCACTCTGGCAGAAATTGCCCGTGCGGTGGGTATCACAGGCGACACGATCA
AAGTAGAAGAAATTGTGGAGGCCGTAAAGAATCTCACAGCGGAGAGCACCGATGA
AGCAAAAGACGAAGAATAA
WW55 3.0
(SEQ ID NO: 162)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTACTCCAGGAGAATTGAACGTCTATAGCAAACAAGAAATTGACCGTATGTTTGTT
AAGAACGTTAAAATGGTTGTTCCTTCTGGTGGTGCAACCCGTGGTTATTTTAAAATT
GCATCCGCAATGATCCCGCAGAGTGGTCGGATGGCGTTTCTGCGAATCTATGGTGGT
AATGGATATAATGTAAACTCATATGATCAAGTTGATTTTCTTGAAATTGTGATTCGT
AGTGGTAATAATAACCCTAAAGGCGTTAGTATTGCTGCATATCGTCGAAATTCTTTG
AACGTCCATGAAGTATTTGCAATTAATACTTCCGGTGATAACTATGACATTTATGTT
AACTATGGTCGCTTCACCGATAACGTTATTGTAGAGTTTGGAAAAACTGTTGACGTC
GCATTGACTGTTCATGATGTTCCTGAATTTTCGGCGACTAAACCAGAAACCGGAACT
AAATTTGATGCTCGTGTTATTACGATGTTCAACACCGAAAACAAAGCCGGAACATTG
ATGTTTGATAATAACAATCAGTTAACCTATGATATTGTTAGCCTTAGCAATGGTCCT
GATGATGTTAGAAATTATCTGCGTAAATTCCGAAGTAAAGCGGGTGAAATGATTTGG
CATGAAACCGTTCAGGGTGCTGTATATCGTCTTGCTACTGGAACTACTGATTCTACG
GAAGTTCTTAGAGTTGATTCTAACAGTGCTCTCCCGGGTAGCTATAAAGGATATGTA
ATTACTGGTAAAATGGAATTGCACGGTAGCGGTAGTGCGATGAATTTACACCGCCA
GACTGGTCAAGCTGCATATATGGCGTGGTGGGATCGTCGTGATGGTAAAAACCAAC
GTAGCGGTTATATCGGTCATGCGGATGGTACTACTGATGGTTTTGTGTGGCGTAATG
ATGTTGGTGCGAACTCATTTGATTTGGAAAGTAGTGGACAAGTAAATTTGACTACAG
GAAAAACAAAAATTGTATATACCAACGGACAATATTATTCCGCTAACTCTGATGCAT
TCCGTATGATTTACGGCAATTATGGCGCATTCTGGCGAAATGATGGTGGTAAAGTTT
ATCTGTTGTCTACTGCCGAAAATGATAGATTTGGTGGATGGAACGGCAACCGACCAT
TCATTTACGACCTGTCAACTGGTAAAGTTACTTTAGGTGGCGACGGTAACGAAGGCG
CATTAGTTCTCGAAAGAGATAGCCGTGCGGCTAGATTTAGCAACAGCGTATTCTTAG
AAAAAGGATTGCTTACTTTCTCTGCGGGTGGGAATCAGTCAATGGATTCTTTCACGA
TTAACCATTGGGGGAATAGTAACGCTGGACGATATAATGTTTTACAATTTGAAGACA
CGAAAGGAACACATTTTACAACCGAACGTAATGCTGATGGTGGATTGCTTGCTCACT
TCCGAGGGGATTTAACCACAGAAGGGAAATTAACGTGGGGTAAGGGTACAGCCACA
TCTAGCTTTAACATTCGTGCATGGGGTAATAGTGATTCCCGTAAACAGGTTTTCGAG
TGTGTAGATGAAAGTGGTTGGCATTGGTATACCCAGCGACCGGGCGGTCCTGGTACT
TCTGCAATTGAGTTTGCCATCAATGGTACTGTTAAGCCTCAAGCAATTCACACTGGC
GGTAATATTCTTTTGAACGGTGCTGATATTGAGTTTCGTCGCACTGGTAATAAGCATT
TGTGGTTTAGAGATCCAAACGGATTAGAATTGGGTTTGATTTATTGTGATGACAACG
GTGTCATTCGTTTTCGTGGTCAGAAACAAGGTCAAGATTGGGTATTTGCCAATAAGA
TGATCCAATTAGGGACCGCTTCTACTGTTGGTGGATCTGGTAACGGTTTGATTCGCG
GACAAGTTCAAGGTGGTGCTTGGGCACAATGGAGAGACCGTGCTGCTGGAATCCTT
GTAGACTGTCAGCAATCTACTGATTCCGCTCATAACATCTGGAAAGCGACTCATTGG
GGAAAATATCATATTGCGGCAATGGGTGTACACGTTCCTAGCGGCACTATAGGTAAT
GCTATGGCACGTCTAAACGTAAATGACGCCAACTTTGACTTTAGCGCCTCCGGTGAC
ATGTCGGCAGGGCGTAACGGTTCGTTTAACGATGTTTATATTCGTTCTGATGCTCGCC
TTAAAATCAATAAGGAAGAGTATAAAGAGAATGCCACCGATAAAGTTAATCGCTTA
ACTGTATACACCTATGACAAGGTTAAATCTTTAACCGACCGTACTGTCATTGCTCAT
GAAGTTGGCATTATCGCACAGGATCTTGAGAAAGAATTGCCGGAAGCAGTAACAAC
CTCGAAGATCGGCGATCCAGATAAACCAGAAGAGATCTTAACAATTTCTAACTCTGC
TGTCAACGCTCTTTTAATTAAGGCGTTTCAGGAAATGAGCGAAGAATTGAAAGCCGT
TAAAGCTGAACTAGCGGAACTTAAAAAGTAA
WW55-G8
(SEQ ID NO: 163)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT 
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT 
CGTGGTGCTATTATCAATTTAAGTTGTCCTCCTGTTTATGACCGCGATGTTACAATGG 
CGGGTAAGGTTAAAGGTAATAATTATATCTTAAGTAAAACCGCTAACTATCTGGAAG 
ATCAGACAGCGAGAGATCTTAACTACTTTGGCGCTTTCCGTACCAATGGTCTTGATG 
GTCTTCTCGAACTCACGCTAAACGTTCCTCACTCTTCCGGTGTCCAACATGGTCGAG 
GATTTACTTTCCAGTATGGGCACACTGGATCGCGTGTAGAAACTTATGGCTATAATA 
AAGAAGGTCAAAAAGCATTTAGTTATAAAATGTATCACGAAGGTGATAAACCAACT 
CCAGGAGAATTGAACGTCTATAGCAAACAAGAAATTGACCGTATGTTTGTTAAGAA 
CGTTAAAATGGTTGTTCCTTCTGGTGGTGCAACCCGTGGTTATTTTAAAATTGCATCC 
GCAATGATCCCGCAGAGTGGTCGGATGGCGTTTCTGCGAATCTATGGTGGTAATGGA 
TATAATGTAAACTCATATGATCAAGTTGATTTTCTTGAAATTGTGATTCGTAGTGGTA 
ATAATAACCCTAAAGGCGTTAGTATTGCTGCATATCGTCGAAATTCTTTGAACGTCC 
ATGAAGTATTTGCAATTAATACTTCCGGTGATAACTATGACATTTATGTTAACTATG 
GTCGCTTCACCGATAACGTTATTGTAGAGTTTGGAAAAACTGTTGACGTCGCATTGA 
CTGTTCATGATGTTCCTGAATTTTCGGCGACTAAACCAGAAACCGGAACTAAATTTG 
ATGCTCGTGTTATTACGATGTTCAACACCGAAAACAAAGCCGGAACATTGATGTTTG 
ATAATAACAATCAGTTAACCTATGATATTGTTAGCCTTAGCAATGGTCCTGATGATG 
TTAGAAATTATCTGCGTAAATTCCGAAGTAAAGCGGGTGAAATGATTTGGCATGAA 
ACCGTTCAGGGTGCTGTATATCGTCTTGCTACTGGAACTACTGATTCTACGGAAGTT 
CTTAGAGTTGATTCTAACAGTGCTCTCCCGGGTAGCTATAAAGGATATGTAATTACT 
GGTAAAATGGAATTGCACGGTAGCGGTAGTGCGATGAATTTACACCGCCAGACTGG 
TCAAGCTGCATATATGGCGTGGTGGGATCGTCGTGATGGTAAAAACCAACGTAGCG 
GTTATATCGGTCATGCGGATGGTACTACTGATGGTTTTGTGTGGCGTAATGATGTTG 
GTGCGAACTCATTTGATTTGGAAAGTAGTGGACAAGTAAATTTGACTACAGGAAAA 
ACAAAAATTGTATATACCAACGGACAATATTATTCCGCTAACTCTGATGCATTCCGT 
ATGATTTACGGCAATTATGGCGCATTCTGGCGAAATGATGGTGGTAAAGTTTATCTG 
TTGTCTACTGCCGAAAATGATAGATTTGGTGGATGGAACGGCAACCGACCATTCATT 
TACGACCTGTCAACTGGTAAAGTTACTTTAGGTGGCGACGGTAACGAAGGCGCATTA 
GTTCTCGAAAGAGATAGCCGTGCGGCTAGATTTAGCAACAGCGTATTCTTAGAAAA 
AGGATTGCTTACTTTCTCTGCGGGTGGGAATCAGTCAATGGATTCTTTCACGATTAA 
CCATTGGGGGAATAGTAACGCTGGACGATATAATGTTTTACAATTTGAAGACACGA 
AAGGAACACATTTTACAACCGAACGTAATGCTGATGGTGGATTGCTTGCTCACTTCC 
GAGGGGATTTAACCACAGAAGGGAAATTAACGTGGGGTAAGGGTACAGCCACATCT 
AGCTTTAACATTCGTGCATGGGGTAATAGTGATTCCCGTAAACAGGTTTTCGAGTGT
GTAGATGAAAGTGGTTGGCATTGGTATACCCAGCGACCGGGCGGTCCTGGTACTTCT
GCAATTGAGTTTGCCATCAATGGTACTGTTAAGCCTCAAGCAATTCACACTGGCGGT
AATATTCTTTTGAACGGTGCTGATATTGAGTTTCGTCGCACTGGTAATAAGCATTTGT
GGTTTAGAGATCCAAACGGATTAGAATTGGGTTTGATTTATTGTGATGACAACGGTG
TCATTCGTTTTCGTGGTCAGAAACAAGGTCAAGATTGGGTATTTGCCAATAAGATGA
TCCAATTAGGGACCGCTTCTACTGTTGGTGGATCTGGTAACGGTTTGATTCGCGGAC
AAGTTCAAGGTGGTGCTTGGGCACAATGGAGAGACCGTGCTGCTGGAATCCTTGTA
GACTGTCAGCAATCTACTGATTCCGCTCATAACATCTGGAAAGCGACTCATTGGGGA
AAATATCATATTGCGGCAATGGGTGTACACGTTCCTAGCGGCACTATAGGTAATGCT
ATGGCACGTCTAAACGTAAATGACGCCAACTTTGACTTTAGCGCCTCCGGTGACATG
TCGGCAGGGCGTAACGGTTCGTTTAACGATGTTTATATTCGTTCTGATGCTCGCCTTA
AAATCAATAAGGAAGAGTATAAAGAGAATGCCACCGATAAAGTTAATCGCTTAACT
GTATACACCTATGACAAGGTTAAATCTTTAACCGACCGTACTGTCATTGCTCATGAA
GTTGGCATTATCGCACAGGATCTTGAGAAAGAATTGCCGGAAGCAGTAACAACCTC
GAAGATCGGCGATCCAGATAAACCAGAAGAGATCTTAACAATTTCTAACTCTGCTGT
CAACGCTCTTTTAATTAAGGCGTTTCAGGAAATGAGCGAAGAATTGAAAGCCGTTAA
AGCTGAACTAGCGGAACTTAAAAAGAATTAA
>WW55 GP38
(SEQ ID NO: 164)
ATGGCAATATCTTCTGGATGGGTAGGATCATCTGCTGTGTCCGAGACTGGTCAACGG
TGGATGAGCGCCGCAATGCAAGCTGTTCGCTTAGGTCGTCCGGCGTATATGTCGGCA
ATGGTCGGACGCTCTAAAGAGATTCATTATAGCATTGGTGCTAGTAACTCTTACAAT
AAAGACACTCTTATTAACTGGATGAAAGCACAAGGATCTACTCCGGTAGTAATTACT
ATCACGGGTAATATTGTTTCCCAATCTACTGGCGTTCCTTGTCTTGATTTCCCTAGCT
CACTGACAAACGAATATGTAACACTCATTATTAACTCTGGTGTTCATGTATTAGGTC
GTGGAGGAAATGGCGGAAGTAACTCTGCTGGTGGAGCAGGAGGAAATGCAATAAAT
AACGGAATTGGAACTCGTTTAAGAATAAACAATAATGGTATTATTGGTGGTGGCGGT
GGTGGCGGTGCTGGTGCTAGATACAATCCTTTCCCTCAAATGGATATGAAATTTGGC
GGCGGTGGAGGCCGTCCATTTGGTGCTGCGGGTGCGGCAGGAGGCGGCGCAGCGGC
AGCATCTGCTGGTACAATTTCTGCCCCAGGTAAAGGCACTGTTTCTGGGGTTCATTA
TGGAGGAGATGGTGGAGATTTGGGAGCTGCTGGCAAATCTTCATATATTAAAGGTG
GTACTGGTGGAACTGTTCACTCGGGTGGTGCTGCGGGTAAAGCTGTTACTGGTAATG
CCCCTCGCTGGGATAAAGTAGGCACGATCTACGGTGCTCGCGTG
WW55 GP57A
(SEQ ID NO: 165)
ATGTCCAATCAGCATGAACAAATGATTAATGTCCTGAAAGTACGTCTGTTTGACACT
CAAGAAAAGGCCGCATTCTTAGAAGGCCAACTGAAAGATCGTGAGCGTGTATTGAT
GGAACTGGTACGCATTCTGGGTATTCAGCCAGACGAAAACGGCACTGTTTCCCTTGA
TGCTATTGTCGAAGAAGTGAAAGCACTTCTCCCTAAAGACGAAGCAGCGGAAGACG
CAGAAGAGGAAGTAGAACTGATCACGGAGGCTTGA
WW34 3.0
(SEQ ID NO: 166)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC 
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG 
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT 
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG 
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT 
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG 
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC 
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT 
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG 
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA 
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT 
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC 
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA 
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG 
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG 
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT 
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT 
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT 
CGTACTCCAGGAGAATTGAACGTCTATAGCAAACAAGAAATTGACCGTATGTTTGTT 
AAGAACGTTAAAATGTCTACTCCTTCTGGTGAAGCAACCCGTGGTTATTTTAAAATT 
GCATCCGCAATGATCCCGCAGAGTGGTCGGATGGCGTTTCTGCGAATCTATGGTGGG 
AACGGATTTAATGTTAACTCCTACGATCAGGTGGATTTCCTTGAAATTGTGATTCGT 
AGTGGTAATAATAACCCTAAAGGCGTTAGTATTGCTGCATATCGTCGAAATTCTTTG 
AACGTCCATGAAGTATTTGCAATTAATACTTCCGGTGATAACTATGACATTTATGTT 
AACTATGGTCGCTTCACCGATAACGTTATTGTAGAGTTTGGAAAAACTGTTGATGTT 
GCATTGACTGTTCACGATGTTCCTGAATTTTCGGCGACTAAACCAGAAACCGGAACT 
AAATTTGATGCTCGTGTTATTACGATGTTCAACACCGAAAACAAAGCCGGAACGTTG 
ATGTTTGATAATAACAATCAGTTAACCTATGATATTGTTAGCCTTAGCAATGGTCCT 
GATGATGTTAGAAATTATCTGCGTAAATTCCGAAGTAAAGCGGGTGAAATGATTTGG 
CATGAAACAGTTCAGGGTGCTGTATATCGTCTTGCTACTGGAACTACTGATTCTACG 
GAAGTTCTTAGAGTTGATTCTAATAGTGCTATACCAGGTAGCTATAAAGGATATGTA 
ATTACTGGTAAAATGGAATTGCATGGTAGTGGTAATTCGATGATTTTACATCGCCAG 
ACTGCTCAAGCCGCGTACATGTCGTGGTGGGATCGTCGTGATGGCAAAAACCAACG 
TAGCGGTTATATCGGTCATGCAGATGGGACTAGTGATGCTATTGTGTGGAATAATGA 
TATTGGACAAAACAGTGCTGTTCTAGAAACATCTGGTCAAATATCTTTCAGAACAGG 
TGCAACCAAAATTGTATATACCAACGGACAATATTATTCCGCTAACTCTGATGCATA 
CCGTATGATCTTTGGTAATTACGGTGCATTCTGGCGTAATGACGGCACTAAAGTTTA 
TCTTCTTTCTACTGCTGAAAATGATAAGTATGGTGGATGGAATGCCTATCGTCCATTC 
ATTTATGATTTAACTTCCGGTAACGTTCAATTAGGCGGTGATGGTAACGAAGATGCA 
TTAACGTTAGAATGTGCTTCTCGTGCCGCTCGCTTTAGTAATGACGTTTACATTAAGA 
AAGGGCTTTTGACTTTCGACGCTGGGCGCGCTGGATCTCGCGATTATATTCGATTTA 
ATCATTGGGGTGATAGTAATAATGCCCGTGATAACGTTTTGTGCATAGAAGATAGTC 
AAGGCCGACATTTTAGCACAGAACGTGCGATGGGTACTGGTGCTCTTAAAGCATACT 
TCTTAGGCGATCTTGAAGTCGGTGGTAAGTTTACTTGGGGTAAAAATACAGCTACAT 
CTAGCTTTAATATTCGTGCATGGGGTAATGATTCCCGTAAACAAGTATTAGAATGCG 
CGGATGAAAGTGGGTGGCATTGGTACACACAACGAACGGGCGGTCCTGATACTTCT 
GCAATTGATTTTGCCATCAATGGTACTGTTAGGCCTCAAGCAATTCACACTGGCGGT 
AATATCACTATCAACGGTGCTGATATTGAGTTTAAACGCACTGGCAATAAGCACATC 
TGGTTTAGAGATCCGAACGGTTTAGAGTTAGGCTTGATGTACTGCGATGATGCTGGT 
GCTATTCGCTTCCGTGGTCAGAAACAAGCCCAGGCGTGGAAATTTGCAGATAAAAT 
GATCCAGTTGGAATCTGGCACTGTATCCGGTGGCGGTAATGGCCTGATTCGTGGTGA 
AGTTGCTGGCGGTAGTTGGGCTAGCTGGCGTGACCGTGCTGCTGGTCTTATGGTTGG 
GTGTCCTCAATCCACCAACTCGGCACATAACGTATGGAAAGCGACGCATTGGGGTA 
AATATCACATTGCAGCAATGGCTGTACATGTTCCTGATGGTACTATTACCAATGCTTT 
AGCTCGCCTAAACGTTCATGACGCCAACTTTGACTTTAGCGCCTCCGGTGACCTGTC 
GGCAGGGCGTAATGGTTCGTTTAACGATGTTTATATTCGTTCTGATGCTCGCCTTAAA 
ATCAACAAGGAAGAGTATAAGGAGAATGCCACCGATAAAGTTAATCGCTTGACGGT 
ATACACCTATGACAAGGTTAAATCTTTAACCGACCGTACTGTCATTGCTCATGAAGT 
TGGTATTATTGCTCAGGATCTTGAGAAAGAATTGCCGGAAGCAGTAACAACTTCTAA 
GATCGGCGATCCTGATAAGCCAGAAGAGATCTTAACAATTTCTAACTCTGCTGTCAA 
CGCTCTTTTAATTAAGGCGTTTCAGGAAATGAGCGAAGAATTGAAAGCCGTTAAAGC 
TGAACTAGCGGAACTTAAAAAGAATTAA 
WW34 GP38
(SEQ ID NO: 167)
ATGGCAATATCTTCTGGATGGGTAGGATCATCTGCGGTGTCCGAGACTGGTCAACGG 
TGGATGAGCGCCGCAATGCAAGCTGTTCGCTTAGGTCGTCCGGCGTATATGTCGGCA 
ATGGTCGGACGCTCTAAAGAGATTCATTATAGCATTGGTGCTAGTAACTCTTACAAT 
AAAGACACTCTTATTAACTGGATGAAAGCACAGGGATCTACTCCGGTAGTAATTACT 
ATCACGGGTAATATTGTTTCCCAATCTACTGGAGTTCCTTGTCTTGACTTCCCTAGCT 
CGTTAACAAACGAATATGTAACATTGATCATTAACCCAGGTGTTCATGTTTGGGGGC 
GTGGTGGTAATGGTGGCAATAACTCCGCTGGTGGCGCTGGTGGTAATGCAATTAACA 
ACGGTATAGGCACACGCTTACGCATCACAAATAACGGCGCTATTTGCGGTGGTGGC 
GGCGGCGGCGGCGGCGGGTATTATTCTCCTTTTTCACAAATGAGATTAACCTTTGGT 
GGTGGCGGTGGGCGTCCGTTTGGTGCTGCCGGTGGGTCTGCTAATATGGAACAGGGT 
GCTACTGCTGGTACTATTTCCGCGCCAGGTAAAGGGTCTGTAAACGGTGTATATAAT 
GGCGGTAACGGTGGTGATGCTGGTGGTGCTGGTGGTAAATGTAATATCCGTGGACA 
GGGATCGGAATATAACGGTGGTGCGGCTGGTAAGGCTGTTACTGGCAATGCCCCTC 
GCTGGGATAAAGTAGGCACGATCTACGGTGCTCGCGTG 
WW34 GP57A
(SEQ ID NO: 168)
ATGTCCAATCAGCATGAACAAATGATTAATGTCCTGAAAGTACGTCTGTTTGACACT 
CAAGAAAAGGCCGCATTCTTAGAAGGCCAACTGAAAGATCGTGAGCGTGTATTGAT 
GGAACTGGTACGCATTCTGGGTATTCAGCCAGACGAAAACGGCACTGTTTCCCTTGA 
TGCTATTGTCGAAGAAGTGAAAGCACTTCTCCCTAAAGACGAAGCAGCGGAAGACG 
CAGAAGAGGAAGTAGAACTGATCACGGAGGCTTGA 
WW14-G8
(SEQ ID NO: 169)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA 
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG 
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT 
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC 
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG 
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT 
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG 
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT 
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG 
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC 
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT 
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG 
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA 
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT 
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC 
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA 
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG 
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG 
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT 
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT 
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT 
CGTAACCAGATTATTGATTTAGGCTTTGCAAAGGGTGGACAAGTTGACGGTGATGTA 
ACTATTAACGGAACTCTGAATTTAAACGGCCCTGAAATTGTTGCCTCCGGTGGTTAT 
ATAGAATTTAACTATCGTACGACAGGTAGTGGCTCTTGGGCGGGTCAGCACGCGGCC 
AAAGCTCCTATTTTTGTTGATTTAAGTGCGGCGTTATCTACTTCAGAATACAACCCAC 
TGTTTAAGCAGCGTTACAAAGATGGAACATTTTCAGCAGGTACATTAGTTACTGAAG 
GTAGTTTTAAATTTCACTATATTAATGAAGCTGGTGATTCGAAATATTGGACCTTTAA 
TCGTAATGGTAATTTTCAAGTTGATACCGGTAGTTTATTTGTATCGGGTGGTAATATT 
TCCGCTTCAGGCAATATCAACTCTGCCTCAGGGTTTGTGTCTGCGCCTCAGATTAATA 
CTAAAAATATTATTTTAGATACAAAAGCATTTGGACAATACGACAGTCAGTCTTTAG 
TTAATTACGTATACCCAGGCACCGGCGAAACAAATGGTGTAAACTATCTTCGTAAAG 
TTCGTGCTAAATCCGGCGGCACTATGTGGCATGAGCTTTGCACTGCCCAATTAGGCC 
AAGCCGATGAAATGTCTTGGTGGACAGGTAATACCCCTCAGTCTAAACAATACGGT 
GTTCGTAACGACGGCCGTTTGATTGGTAGAAATAGCCTTGCATTAGGTACTATGACT 
ACCGATTTCCCATCTAGCGATTATGGTAATACCGGAGCTATGGGTGACAAATACCTA 
GTTTTAGGTGATACTGCAACCGGTTTAAAATATATCAAACAAGGCAATTTTGATTTA 
GTTGGTGGTGGATATTCTGTTGCGTCAATTACCACAGACGGTTTCCGTGGCACAAGT 
AAAACCTTATTTGGTCGTAGTAATGACCAAGGTTTAACATGGCTTCTTCCTGGTCAA 
AACTCTGCAATGGTTTCTATCAGAACCGAAATAGATGGTAATAACTCTGGCGATGGC 
CAAACCCATTTAGGTTATAATTCTAATGGTAAACTTTATCATTATTTCCGTGGTACCG 
GTCGTGTAGCCATTTCTATGGCAGAAGGTATGATTATTGAACCTGGTATTTTAAATA 
TTAAGACCGGGGTTAACGAATTAAATCTTAGAGCAGACGGCACAGTTTCTACTACAC 
AGCGTTTAATGGTTAATAACGGCTTAGTTCTTAACGCAAACAATAATACTTCTGCAT 
TGGCATTAACTGCTCCTACCGGTGTTGATGGTACAAAAACCATTAACTGGGACGCTG 
GTACCCGAAATGGCCAGAACAAAAATACCGTTACCATGAAAGCATGGGGTAACTCA
TTTAACGCGGGTGGTGGTAATAGAGAAACTGTATTCGAAGTATCAGATTCACAAGG
ATATTATTTCTATGGCCAACGTACTAATCCGGCTTCCGGTGAAACTGTAGGCCCTATT
AACTTCAAGTTCAACGGTTCTGTTGAAACAGGTCATTTTTCTAGTCTCGGAAATATA
AGTGCATCTGGTACCGGTTCTTTTGGTGGCAATGTTACCATGACTAATGGCCTGTTTG
TCCAAGGCGGCGCTTCAATTAATGGCCAAGTTAAAATGGGTGGTACTGCTGACGCAT
TAAGAATTTGGAACGCTGAATATGGTATGATTTTCCGTCGTTCAGAAACGGGTTCTT
CTGCTTCATTCCATCTTATTCCTACCCTTCAAAACGCCGGTGAAAATGGCGGAATAA
GTGACCTTCGTCCACTATCTATCAATTTAGCTAGCGGCACGGTTATAATGGGTAATA
AAAGCACAGGTGGCCCACTTTTCACAGTAGACAACGTAAGTAAATTTGTTCAAACCG
ACTGTAGATTGCGTGTTAATATGGATTCTGATGGTATTGTTTTGAATGCTTCATCTCA
AGCAGCATCCAACTTTATTCAAGGACGTAAAGCAGATGTTACAAAATGGTATCTAG
GTATTGGCGATGGTGGCAACGTCGTTCGTATGCACAACTATACTTATTCACATGGTA
TTGCATTAAACTCTGATACCGTTGATATAACCAAGCCTCTTAAAATAGGTTCTGATA
TTCGTATCGGTACTGATGGGAATATTATAGGCAGTGCTACTTTAGATAACTTTAAAA
ACCTGAATACAACATTAGACCATAAAGTTAATATGGGCGGTTGGTCCGGCGGTGCTA
CTACAGGTTGGTATAAATTTGCTACTGTAGAAATTCCACAGGCAACAGGCACGGCAT
CTTTTAAAATATTTGGCGGTTCCGGGTTTAATTTTAAAAGTTACGGTCAGGCTTCAAT
AGCTGAAATAATTCTTAGAACCGGTAATAATAACCCTAAAGGCCTTAATGCCACGTT
GTGGAATAGGACTTCTGAAGCTATTTCCCAGATTGCTTCGGTTAATACAAGCGAAGA
TATCTATGATATTTACGTTTACTTAGGTGGGTATTCTAATTCTTTGGTGGTAGAATAT
ACCTGCAGCAGCAATAGTAAAGTAACCGTAGTAGGTATGGATGGTGGTGTCCAGCC
TTTGGTAGAAACATTACCTGAAGGTCATGTTGTAGGTAAATCTGTAAGAATGCTGAA
CAACCTTGACGGAATGTTTGCCGCTGGCGAATCGGATATTGTTACTCGTGGTGAATA
TGTTACCAATAACCAAAAAGGTATGCGTATTAAATCTAAAGGTAATGATTTAGATTC
TAATGCTGCTTTACTTAGAAACGACGGTGGAAGTTTTTATATTTTAGCTACAGATAA
AAATACGACAGAAAAACCCGATGCGGCTAATGGTGATTGGAATGGCTTAAGACCTT
TCTCGATTAATATGGCTGATGGTCGCGTTGGTATGAACCACGGATTGAATATTACTG
GCGGTGGTCTGAACGTTACCGGCGGTAATACTAACCTTGGTAATATTACATCTCGTG
TAGTTTCTTCGGCACGCGCCGGGTCCGGTTGGGGTGATAACTCTGATGCTATGAAAT
CCAAAATTACCTTTATGGCTGACCACGGTGATTTATCTAATTCAGGCAGTTATTATCC
TATCGTAGGCGCATACAGCAACTATGGTTCAGCGGGTTATCGTCAAACCTTTGAATT
TGGATGGGTCGGCTCTGGTAGCACCGCAAATTGGCGAGAAGGTATTATTCGTATTCG
CGGTGATAATGCTAACGGCCAGCAAGCAAGATGGCGCTTTACAATGGACGGTATTTT
AGGTTGCCCTGGTAAAGTAGAGATGCCAGAAACAAGCGCATTTGGTATCAACACAA
CAAATGGATTTGGTGGTAACTCGATTGTAATTGGTGATAGCGATACTGGTTTTAGAC
AAGTCGGTGATGGGCTTTTAGAAGTTTGGACTAACGCCTCACGCCGAATGAGATTCC
AAGGCGGTGATACCTATTCAGATATGAATATTAACGCCCCGAACGTTTATATTCGTT
CTGATATTCGTTTGAAATCTAACTTCAAACCGATTGAAAATGCTCTTGATAAGGTTG
AACAGCTAGACGGTTTAATCTATGATAAAGCTGATTATATTGGCGGCGAAGTTGTTC
ATACCGAGGCCGGTGTTATTGCTCAGAGTTTGGAAAAAGTATTGCCTGAAGCTGTCC
GTGAAGTTGACGACATTAAAGGTAACAAAGTTCTTACCGTTTCAACCCAGGCACAA
GTTGCTCTGTTAATTGAAGCAGTTAAAACTCTGTCGGCTAAAGTTAAAGAACTTGAA
GCAAAACTTAATTAA
WW14 GP38
(SEQ ID NO: 170)
ATGGCAATTGTAGGTGTTCCTGGTTGGATTGGACAATCTGCCGTAGATGAAACGGGA
CAACGTTGGATGGATGCCGCTATGCGCGATGTGCGAGTTGCAGTACCCGGTTGGATG
GGGTCGATGGCAGGACAATCAAAAGAAATTTATCTATCTATAGGGGCTAATAACTCT
TATGATAGAAACTCCCTTATTAACTGGATGAGGGCTCAAGGTGGCGCGCCTGTAGTT
ATTACAATCACCGGTAACTTAGTATCCAATAGCACCGGTAACGCTTGTTTGGAATTT
CCTAGCAATCTTCCTAACGCGTATATTCAACTTATCATTAATAGCGGTGTGACTGTTT
ATGGCCGAGGAGGTAATGGTTCTACTAATGGTTCGGCAGGTGGAAACGGTGGTACA
GCTATCCATAACGCAGCCGGAACTAAACTCCGTATTCGTAATAACGGCGCTATTGCC
GGTGGTGGTGGTGGCGGTGGCGCAGTATCATTGCAAAATAGCTACCCGACTAATGG
TACATGCGGTGGTGGTGGTGGTAGACCATTTGGCGTAGGTGGTAAAATAGGCTCTGA
CGCTATATTGTCCGGTTCGAATGCGTCTTTAACAGCTGCCGGTACAGGTGGTGCTAC
AGTCCAATATGGTGGAGGTAATGGCGGTAACGTTGGAGCTGGCGGTGGACGAGGAT
GGGGCAAAAATGTTTATACCTCTGCAGGTGGCTCAGCTGGTGCTGCTGTCACTGGCA
ATGCTCCTAACTGGCAAAACGTAGGAACTATTTACGGCTCAAGAGTCTAG
WW14 GP57A
(SEQ ID NO: 171)
ATGTCTGAACAAACTATTGAACAAAAACTGCAAGCCGAAATCGTAGCTCTTAAATCC
CGCATTCTGGACACCCAGGATGTTGCAGCTCAAGCTCAACAGGAATCACGTATTCTG
CAGGATGCGCTGAGTAAAATCGCTGCTCGCTTAGGCATCACCGGTGACCAGATTCAG
ATTGAAGACCTGATTGCCGCTGTTCCTGATTTGACCGCTGAAAGTGCTGACGAAGAA
TAA
WW170-G8
(SEQ ID NO: 172)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTGGTGCTATTATCAATTTAAGTTGCCCTCCGGTGTATGACCGCGATGTTACAATG
GCGGGTAAGGTTAAAGGAAATAATTATATTTTAAGTAAAACCGCCAACTATCTGGA
AGATCAGACAGCGCGAGATCTTAATTACTTTGGTGCTTTCCGAACTAATGGACAAGA
TGGTCTTTTAGATCTAACTCTTAATGTTCCTCATTCTGCTGGCGTTAATCATGGTCGA
GGATTTACTTTCCGTTATGCGACTGGCGGATCTCGTGTTGAAACCTATGGGTATAAT
GCACAGGGACAAAAAGCATTTAGCTATAAAATGTATCATGAAGGTGATAAACCTAC
CCCATCGGAATTGAACGTTTATAGCAAACAAGAAGTTGACCGTATGTTTGTTAAAAC
CGTTAAACTTGCTACAGTTCCTGTTGATATCGTTGACGGTTATTTTAAATTAGCAACT
GCGATGATTCCGCAAAACGGTCGTAGCGTATTTTTCCGTATTCATGGTGGTAACGGA
TATAACGTTACTGCATACGATCAAGTTGATATTGTAGAAATTGTTATTCGCAGTGGA
AATAATCGTCCTAAAGGTGTTAACGTTATTGCATACCGCCGAAATACAAACAAAGC
ATTTGATGTTTTGGCTGTTAATACTTCTGGTGATAACTATGATATCTACGTGAAATAT
CAGCGTTACACTGATAACGTTATTGTTGAATTTGGTAAAAGTGTTGATGTTGATCTG
GTAGTCCATGACGTTCCAGACTTTGTTGTTGATCGTCCTGTTGGCGATAATGTTATTG
GCGGTCGCGCGGTAACTCTTTTCAACACCGAAAACAAACGAGGTGTGTTGAGTTTTG
ACGATAACACACAAAATAGTTATGATATTGTTCACTTGAGTAATGATAGGGGTACTG 
GACGAAAATATATTCGTAAATTCCGTAGCAACTATAACGAAATGATCTGGCATGAG 
ACGGTTCAAGGTTCTACTTATCGACTCGCCACGGGTAGCACAGATGCCCAGGAGATT 
CTATCCGTTGAATCTAGTAGCTCTATTGCTGGAACTCATAAAGGTAATATTCTTTCTG 
GTCGAATGATGTTGGGTGGCGGTAGTAATGTTATTACCTTGCGGCGTCCTGCTGGTC 
AATCCAACCATATTGCGTTTCAAGATAATCGTACTGGATCTATTACCCGTCAAGGGT 
GGATCGGTTATGGTAATGCTGATACTAACGTTTTTGAATGGTATAGTGATGTAGGTG 
GTACTTCTATTCGTCACCACATCGACGGACAGATCGAACTTGCAACCGGTAACACAA 
AACGCGTTTATACTAACGCTCAATTCATCTCAATGAATAGCGACGCCTACCGTATGA 
TCTTTGGTAATTACGGTGCATTCTGGCGTAATGACGGCACTAAAGTTTATCTTCTTTC 
TACTGCCGAAGATGATAAATTTGGCGGGTGGAATGGAAACAGACCGTTCATTTACG 
ATTTGACCAACGGTAAAGTTACTTTAGGTGGTGATGGTAACGAAGGTGCATTAGTTC 
TCGAAAGAGATAGCCGTGCTGCTCGATTTGCTGGTGATGTTTATGTAGAAAAAGGAT 
TTCTTCATTTTTCTAGTGGGCGTCAGGGTGCTAGCGGTTTCATGAAAATAAACCATTT 
GGGTGATATTGCCAGTGGACGACACAACATTCTTCAAATAGAAGACCCTACAGGTA 
TACATTTCTCTACTGAACGCAATGATGAAACCGGAAATATTACTGCACGTTTTAAAG 
GCTTTGTACGTGTAGAAGCTGGTGAAATTGCATTTGATGCTAATCGGGGGTCGCAGT 
CTCAATTTACCTTACACACATGGGGTAACGAGCAACGCAAACAGGTTTTTGAATGTA 
AGGATGCTACAGGTTATCACTGGTATACTGAACGTACTCAGGGTGGCACTGGAAAT 
GTTCTGTTCTCTATGGCTGGTAGTCTAAACGTTACTAGCAATATCACAACAACTGGT 
GCTGATATTACGTTTAAACGCGCTGGCAATAAGCACATCTGGTTTAGAGATCCAGAC 
GGTTTAGAGTTGGGCTTGATGTATTGCGATGATGCTGGTGCTATTCGCTTCCGTGGTC 
AGAAACAAGCCCAGGCGTGGAAATTTGCAGATAAAATGATCCAGTTGGAATCTGGT 
ACTGTATCTGGTGGCGGTAATGGCCTGATTCGTGGTGAAGTTGCTGGCGGTAGTTGG 
TCTAGCTGGCGTGACCGTGCTGCTGGCCTTATGGTTGGGTGTCCTCAATCCACCAAC 
TCGGCACATAACGTATGGAAAGCGACGCATTGGGGTAAATATCACATTGCAGCAAT 
GGGTATACATGTTCCTGACGGTACTATCGGTAACGCTCTTGCTCGTCTCCATGTTCAT 
GATACTAACTTTGACTTTAGCGCCTCCGGTGATATGACGGCAGGTCGTAACGGTTCG 
TTTAACGATGTGTATATTCGTTCTGATGCTCGCCTTAAAATCAATAAGGAAGAGTAT 
AAAGAGAATGCCACCGATAAAATTAATCGCTTGACGGTATACACCTATGACAAGGT 
TAAATCTTTAACCGACCGTACTGTCATTGCTCATGAAGTTGGTATTATTGCTCAGGAT 
CTTGAAAAAGAATTGCCGGAAGCAGTAACAACTTCTAAGGTCGGCGATCCTGATAA 
GCCAGAAGAGATCTTAACAATTTCTAACTCTGCTGTCAACGCTCTTTTAATTAAGGC 
GTTTCAGGAAATGAGCGAAGAATTGAAAGCCGTTAAAGCTGAACTAGCGGAACTTA 
AAAAGAATTAA 
WW170 GP38
(SEQ ID NO: 173)
ATGGCAATATCTTCTGGATGGGTAGGATCATCTGCGGTGTCCGAGACTGGTCAACGG
TGGATGAGCGCCGCAATGCAAGCTGTACGCTTAGGTCGTCCGGCGTATATGTCGGCA
ATGGTCGGACGCTCTAAAGAGATTCATTATAGCATTGGTGCTAGTAACTCTTACAAT
AAAGACACTCTTATTAACTGGATGAAAGCACAAGGATCTACTCCGGTAGTAATTACT
ATCACTGGTAATATTGTTTCCCAATCTACTGGCGTTCCTTGTCTTGACTTCCCTAGCT
CGTTAACAAACGAATATGTAACATTGATCATTAACCCCGGTGTTCATGTTTGGGGGC
GTGGTGGTAATGGTGGCAATAACTCCGCTGGTGGTGCTGGTGGTAATGCAATTAACA
ACGGTATAGGCACACGCTTACGCATCACAAATAACGGCGCTATTTGCGGTGGCGGT
GGCGGTGGCGGCGGTGGGTATTATTCTCCTTTTTCACAAATGAGATTAACCTTTGGC
GGTGGTGGTGGGCGTCCGTTTGGTGCTGCCGGTGGGTCTGCTAATATGGAACAGGGT
GCTACTGCTGGTACTATTTCCGCGCCAGGTAAAGGGTCTGTCAACGGTGTATATAAT
GGCGGTAACGGTGGTGATGCTGGTGGTGCTGGTGGTAAATGTAATATCCGTGGACA
GGGATCGGAATATAACGGTGGTGCGGCTGGTAAGGCTGTTACTGGCAATGCCCCTC
GCTGGGATAAAGTAGGCACGATCTACGGTGCTCGTGTGTAA
WW170 GP57A
(SEQ ID NO: 174)
ATGTCCAATCAGCATGAACAAATGATTAATGTCCTGAAAGTACGTCTGTTTGACACT
CAAGAAAAGGCCGCATTCTTAGAAGGCCAACTGAAAGATCGTGAGCGTGTATTGAT
GGAACTGGTACGCATTCTGGGTATTCAGCCAGACGAAAACGGCACTGTTTCCCTTGA
TGCTATCGTCGAAGAAGTGAAAGCACTTCTCCCTAAAGACGAAGCAGCGGAAGACG
CTAAAGAGGAAGTAGAACTGATCACGGAGGCTTGA
WW202-G8
(SEQ ID NO: 175)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAA
CTGCACCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGG
TGGGCTCAGAGAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGT
CAGTACAGTGTCATCCTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATC
ACCGTGTATGAAGATTCACAACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACG
GAGGATGATGCCCGGCCGGAGGTGCTGCGTCGTCTTGAACTGATGGTGGAAGAGGT
GGCGCGTAACGCGTCCGTGGTGGCACAGAGTACGGCAGACGCGAAGAAATCAGCCG
GCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCCCTTGTGACTGATGCAACTGACT
CAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATCGTCAGCTCAGGAAGCG
TCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAAAAAAGTGCCGC
AGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGAAAACGT
CAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGCG
GCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGA
GGCAGCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCT
CGGCAACGGCGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGC
CAGGTCATCTGAAACAGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAA
CAGCGGCGGCGGGGAGTGCGTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGG
AAGTGCGGTATCAGCATCGCAGAGCAAAAGTGCGGCAGAAGCGGCGGCAATACGTG
CAAAAAATTCGGCAAAACGTGCAGAAGATATAGCTTCAGCTGTCGCGCTTGAGGAT
GCGGACACAACGAGAAAGGGGATAGTGCAGCTCAGCAGTGCAACCAACAGCACGT
CTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGTAATGGATGAGACTAAT
CGTGGGCAAATTGTTAATTTAAGTTGCCCTCCTGTTTATGACAAAGGCTTTGATGTA
AGAGGCCGCGTGGTTGTGGATGACCTTGTGTGGAGTAATACCGCAAACTATTTCGAT
GACCCGACCGCACGAAATCTTGATAAATTTGGGGCATTTCGTACTAATGATATGGAT
GGTCATCTAGCATTTGCTTTGCATATTCCCCATCCTAGCGGTATAAATCATGCTCGTG
GGTTTGATTTTACTTATGGTTCTAACGTTGTTCCTACTGTAAAAACCTATGGTTATAA
CGCTGATGGTGTATTGGCATATTCATATCGCATGTATCACGAAGGTGATAAGCCTAG
TCCGTCAGAATTAAATGTATACAGCAAACAAGAAGTAGATCGGATGTTCCAAAAAA
CCATCAACTTTGGTGTAGAAACTGGATGGTTTAAAATTGCTACAGCATTTATTCCGC
AAAATGATGGACGTAGCTTGAAAATTAGATTGGTTGGTGGAAATGGGTGGAACGTA
GGCCAAACGGGACAATGTAATATTATTGAACTTGTTATAAGGACTAGCAACGGTTCC
CCTAAAGGAATTAACTTTGTTGCATATCATCATGTTTCTGGTTACGAAAATCAATTTT
GTGCCATTAATACAGGTGATGACACTTATGATATCTATGCATACTACTACGAATTTA
CTAATATGGTAATGGCTGAATATCAAGCGTCCAGCGATGTTAATTTAACTGTATTTG
ATCGACCTGAATATGTAGGCGAAAAACCTGTAGCCGAACATATATTCGATGCATATA
CAATACACTCCTTTAACAGTTTCAGTAACCGTGGAACATTAAATTTTGCTGGCAACC
ATCAAGGACAATATGACATTGAGCATATGAACGAACAACCGACAAATGCTAAAAAG
ATGTTGCGTCGGTTTCGAAGCTCTGCCAGCGCGACAATCTGGCATGAAACCGTTGAT
GACCAGAATTATCGTCTTGCCACTGGAGGTACAGACTCAGTTCAACAATTATTGTTG
TCTTCTGGGACTGGTTTGCATATTCGTAGATTGACCATCGATGGTGGCTTAGGTTCCG
GTTCTAATGCTGGTATTGATATTCGTCGAGGACCAAACGAATCAAGCCATTTTAATT 
TTATGGATTATCGCACTGGTCAAGATGTTCGTAATGGTTGGTTTGGTTTTGGTGATTT 
GACGACCAAAGATTTTATTTGGTGGAACGATAACGGTCAAAACTCGATAAACTTGAT 
CGAAAACGGTGAATTACATATTACTGGCGGTAGAGGCCAGAAAATTGTAATGAATA 
GCGAAGTTGCATTATCTGAAAATGCTCGTTTGGCTGTCAAAGGTGGTAACTATGGTT 
TAATCCTTCGTAATGATGGGACTGGTTTCCATATACTGACTACCGATTTAAAAGATT 
CTTTTGGTAGTTGGAATAATCGCAGACCATTCAGCTATAATTTTGCGGACGGTGGAT 
TATATTTAGGTGGTACTGAAACTGCTCGTTGTTTGCATCTTGGAATTGATGGTAGCAC 
TCGTCTAGAAGACAACCTTTTCTTTAAAGCTGGTTCTCGTCAATCTATGGACTATATG 
GAACTCGTCCATTGGGGGGCAAGCAATACAGGTCGAAATAACGTTTTAAGTCTTCGT 
GACTCAAAAGGATTTTTAGCAGAATTTGAACGCGTGGGGGGGACTGACGGCGTTAA 
AACCAGATTCTTTGGCGAAACATTCACTGACGGTACATTATACCTAAATCAGATGAA 
TAATAGCTCTGAACGATTCTCTATCAATAACTGGGGAAATTCAGAAGTTGGTCGCGC 
GGCAGTAATGGAAGTTGGCGATTCCAAAGGTTATCACTTCTATGCGGAACGTAGAA 
CAGATGACACCGTTTTATTTGATGTATCTGGTGCTTTGACCGTGCATGGACCTAACG 
GAATAACCGTCAAAAACTCAACTGGTGCACGCCATATCTGGTTTAGAGATGATAGC 
GATACGGAAAAGGCTGTTATCTGGGCTACAGATGATGGTATGTTACATATACGAAAT 
AATCATGAGGGTTCATTTGCTCATCACTTCCAGGGCGCAATGATTAAACTGGAAGGG 
CGTGTTCCTTATGGTGCAGCAAAAGGGCTTATTCGAGGCGAGGTAGACGGTGGTGC 
ATATGTTGCATGGAGAGATCGCCCTGCTGGTTTGTTGGTTGACTGCCAGAAAAGTAT 
TGACAGTGCTCATGCTGTTTGGAAAGCGGTTGATTGGGGGCGTCAATATATCGCTGC 
TATGGACGTTCATTGTCCGGGTGATGGTAATAATACTGCGGCAGCGGTTCTTCATGT 
TCAGGCTGCTGATTATCAATTCCATGCAAGCGGAGAATTTCATGCCTCTGGTAACGG 
GAACTTTAACGATGTGTATATTCGTTCAGACCGTCGCCTTAAAGACAATATAGAAGA 
TTATACAGGAAATGCGTTAAGTTTGATCGGCAAACTGAAAGTGAAAACTTACGATA 
AAGTTAAATCTCTTAAAGACCGTGAAATTATCGGTCACGAGATCGGCATTATCGCAC 
AGGATTTACAAGAAATATTACCGGAAGCTGTAAAATCTTCAAAAGTTGGCAATCTTG 
ATAATCCAGACGATGTTCTGACAATTTCTAACTCTGCTGTGAATGCTCTTTTAATTAA 
GGCTATTCAGGAAATGAGTGAAGAAATTAAAGAATTGAAAACTCCTTTCTTTACTAA 
AATTGCTCGCAAAATTAGTAAATATTTTAAATTCTAA 
WW202 GP38
(SEQ ID NO: 176)
ATGGCAGTAGTTGGTGTTCCTGGTTGGATTGGAAGTTCAGCCGCAAATGAAACAGG 
GCAACGATGGATGAGTCAAGCGGCTGGTCAATTAAGATTGGGTGTTCCTTGCTGGAT 
GAGCCAATTCTCCGGTCGTTCAAGAGAAATTATTCATACACTTGGAGCAGACCATAA 
CTTCAATGGTCAGTGGTTCCGTGATAGATGCTTTGAAGCAGGTAGTACACCTATAGT 
GTTTAATATCACCGGAGATTTAGTATCATATTCTAAAGATGTTCCTTTATTCTTTATG 
TACGGAGATACACCTAATGAATATGTTCAGTTGAATATACATGGCGTAACGATGTAT 
GGTCGTGGCGGGAATGGCGGTAGCAATAGTCCTGGATCAGCTGGGGGTCATTGTATT 
CAAAATGATATTGGTGGGAGACTAAGAATTAATAATGGTGGAGCTATTGCAGGTGG 
CGGTGGCGGTGGCGGTGGCGGGTATTATTCTCCTTTTTCACAAATGAGATTAACCTT 
TGGCGGTGGCGGTGGGCGTCCGTTTGGTGCACCCGGCGGATCTATTGATATGCAATC 
AGGCGCAACTGCTGGTACTCTTTATGCTCCTGGATCGGGGTCCGTGAACGGTATCTA 
TAATGGCGGAAGCGGTGGTGAGGTAGGCGCCGCAGGAGGTAGATGTAATATTCGTG 
GTCAAGGATATGAATACAATGGCGGCGATGCTGGTTATGCTGTTATAGGTTCTTCTC 
CAACGTGGCAAAATCGCGGAGCTATTTACGGACCTGCTGTTTAA 
WW202 GP57A
(SEQ ID NO: 177)
ATGTCCAATCAGCATGAACAAATGATTAATGTCCTGAAAGTCCGTCTGTTTGACACT 
CAAGAAAAAGCCGCATTCTTAGAAGGCCAACTGAAAGATCGTGAGCGTGTATTGAT 
GGAACTGGTGCGTGTTCTGGGTATTCAGCCAGATGAAAATGGCACTGTTTCCCTTGA 
TGCTATCGTCGAAGAAGTAAAAGCACTTCTCCCTAAAGACGAAGCAGCGGAAGACG 
CTAAAGAGGAAGTAGAACTGATCACGGAGGCTTGA 
PAYLOADS
p7.3 (p513)
(SEQ ID NO: 178)
CCTTTAGGGAAATATGCTAAGTTTTCACCGTAACACGCCACATCTTGACTATATATGTGTAG
AAACTGCCGGAAATCGTCGTGGTATTCTGACCAGAGCGATGAAAACGTTTCAGTTTGCTCAT
GGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGCC
ATACGAAACTCCGGATGTGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAA
ACTTGTGCTTATTTTTCTTTACGGTTTTTAAAAAGGCCGTAATATCCAGCTGAACGGTTTGGT
TATAGGTGCACTGAGCAACTGACTGGAATGCCTCAAAATGTTCTTTACGATGCCATTGACTT
ATATCAACTGTAGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTTGCGAAATCT
CGATAACTCAAAAAATAGTAGTGATCTTATTTCATTATGGTGAAAGTTGTCTTACGTGCAAC
ATTTTCGCAAAAAGTTGGCGCTTTATCAACACTGTCCCTCCTGTTCAGCTACTGACGGTACTG
CGGAACTGACTAAAGTAGTGCGTAACGGCAAAAGCACCGCCGGACATCTGCGCTAGCGGAG
TGTATACTGGCTTACTATGTTGGCACTGATGAGGGTGTAAGTGAAGTGCTTCATGTGGCAGG
AGAAAAAAGGCTGCATCGGTGCGTCAGCAGAATATGTGATACAGGATATATTCCGCTTCCTC
GCTCACTGACTCGCTACGCTCGGTCGTTCGACTGTGGCGAGCGGAAATGGCTTACGAACGGG
GCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGTCGCGGCA
AAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCA
GTGGTGGCGAAACCTGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTCCCTCG
TGCGCTCTCCTGTTCCTGCCTTTCGGTTTGCCGGTGTCATTCCTCTGTTACGGCCGAGTTTGTC
TCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATGCAC
GAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCC
GGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGT
CTTGAAGTCATGCGCCGGATAAGGCTAAACTGAAAGGACAAGTTTTGGCGACTGCGCTCCTC
CAAGCCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGC
AAGGCGGTTTTTTCGTTTTCAGAGCAAGAGATTACGCGCAGACCAAAACGATCTCAAGAAG
ATCATCTTATTAATCAGATAAAATATTTCTAGATTTCAGTGCAATTTATCTCTTCAAATGTAG
CACTTTATAGCTAGCTCAGCCCTTGGTACAATGCTAGCGTTTTCATTAAAGAGGAGAAAGGA
AGCCATGAGTAAAGGTGAGGAATTATTTACTGGTGTTGTTCCGATCTTAGTTGAACTGGACG 
GCGATGTTAACGGTCATAAATTCAGTGTTCGTGGTGAAGGTGAAGGTGATGCAACCAACGGT 
AAGCTGACCCTGAAATTCATCTGCACTACTGGAAAATTACCAGTACCGTGGCCTACTCTGGT 
GACTACCCTGACCTATGGTGTTCAGTGTTTTTCTCGTTACCCTGACCACATGAAGCAACATGA 
TTTCTTCAAATCTGCAATGCCGGAAGGTTATGTACAGGAGCGCACCATTTCTTTCAAAGACG 
ATGGCACGTATAAAACCCGTGCAGAGGTTAAATTTGAAGGTGACACTCTGGTGAATCGTATT 
GAACTGAAAGGCATTGATTTCAAAGAGGACGGCAATATTTTAGGCCACAAACTGGAATATA 
ACTTCAACTCCCATAACGTTTACATCACCGCAGACAAACAAAAGAACGGTATCAAAGCTAA 
CTTCAAAATTCGCCATAACGTTGAAGACGGTAGCGTACAGCTGGCGGATCATTACCAACAGA 
ACACTCCGATTGGAGATGCTCCTGTTTTACTGCCGGATAACCACTACCTGTCCACCCAGTCTA 
AACTGTCGAAGGATCCGAACGAAAAGCGCGACCACATGGTGTTATTAGAGTTCGTTACCGCT 
AGTGGTATCACGCACGGTATGGATGAACTCTACAAATAAGTCAGTTTCACCTGTTTTACGTT 
AAAACCCGCTTCGGCGGGTTTTTACTTTTGGGTTTAGCCGAACGCCCCAAAAAGCCTCGCTTT 
CAGCACCTGTCGTTTCCTTTCTTTTCAGAGGGTATTTTAAATAAAAACATTAAGTTATGACGA 
AGAAGAACGGAAACGCCTTAAACCGGAAAATTTTCATAAATAGCGAAAACCCGCGAGGTCG 
CCGCCCCGTAACCTGTCGGATCACCGGAAAGAACCTGTAAAGTGATAATGATTATCATCTAC 
ATATCACAACGTGCGTAAAGGGACTATAACAAGACGCAAACGGAGGTAGGCTCACTCCTAC 
TTCGGAAACTTAACCGAAGAACTAGGACGGTATTGTTTGCGCTTGGAATTGGCCTTGAAGTA 
AGTCAGGTTTTGACGGAACGATTAGTTACAGGGGGGGAACAGTCGTTGGTCGCCACCAAGT 
CGATTTTTGGCTTACCTCTTATCTCGTAGTTGGTGAGGGTTGGGATTCACGGGACGAGATCCA 
GCCTAAGTATATTGTCACTTCTGATTCGTTCGATCACTTACTCCCCTTACTTATCCTGCGGCTA 
CTGTTTCCGCTGGCTCGTAAGCTCTACGTTCGGCAATCTACCCGCGAGGTCAGACGTGACAC 
TCTTAAACTAAAAATTGGTAGCTTCTTTGGCTGAATTGCTGGATCTTATTCGTTCACCCAATA 
AAACGGTACAGCTTCAAGCAATATCCTCAGTAAGTTAATACCCGTTGTACTATTACTTTCAC 
GACCGTTCGACGTTCCCGCTCTATTTATTAAGAGCTGTCACTTCGAGTCTTTAGCTCACTTAG 
GAATTAGCTGAGTTTAGGCTCAGCCCTCTTGGGTTGCTTGTACTTTCAGAGTTATTCGCACGG 
CTGGTTTTGTCGAGTGGGGAATTGTGGTTGACCGAAAGTCCGCTATCCTTCAACGCCGAATC 
AGCTCTTGCCCTTTACTATCTTCAATCTCTTGGAGGCTATTACGGGCGGGGGCAAGAGATTA 
GAACTGCAAGACACCCGTTGATAATCGAGTCGCTCGATAGATTGTCGAGAGCCGGAGAGAT 
TAGTACGTTATTCAAGGCAATACGTGCAGGGTTAATCTGGGCGCGTTGTAGTCTACGCTGGC 
GTAAGTCCCCAATAACACGCTCGTCCGGCGAGTCACGATCCTCTAGGCGGTGTTCAACGCGT 
ACGCCAGCTATTTGGGATACTTAGCTACGTTACACGTAAGAATATCTTAGCGGAGGATCGCC 
CTGCTTCCGCTTGGACGGATAAACGGGAGAGTGGGCGCGTATAGCGCAGGCGGTGTGAAGG 
CTTTTAAGTAATTCTAGCCCTCTTTGAACGGTATTTCCCAATTTGGAGATTACCGGATAGCGC 
GTTTAAATGAGTGTCAGAGAAACGGAAGCCGAAGTCTTTCCATTCCGGATGTTTGGAAATGC 
TCTGTTTATAGAAGTCGATGAACTTACGGCAGTCCTCTATATTAAATTCGAATTTTTCATACC 
CTTTCTGCGGGCTACCGTTTTTAGTGTGCGTGCTATGATTGCGGATGCGCAGAATATCCTCAG 
ACGGGTTGTAGAATTTGATGCTTTTCGCGGAAAAGAACACTTTCGGTAACATTTTATTCGCA 
CCCGGCAGGAGCTTGTACACGATTTTCTTATAGCCTTCACCCTTGTTTTCTTTGATCGCTTTAT 
CGTCGAAGATCTTGTTGTTCTTCTTGTTCATTACGCCCAGATAGTATTTGTCGTCTTTGATGA 
ACAGGATTGCGGTGTTGTCCGGCTCTTTGTTCTTATCCCAGCCGTTCGCCAGCGTGCTGTTTT 
CGAAGTTCAGTTTGAATTTCTCGTCAGAGTAAGGCTTCTGCGTGATGTAGTTGCGGATTTTAT 
TGTAGAGAGGGACGATGTTTGCCAGTTCGAAGTAACATTCTTCGAACACCAGATAGAAGTGT 
TCATCTTTATCCAGAATGTTCGCCTTGTCCTCGCTCTGGCTGATGTGGAAGATTTTGAGCTTG 
TGTAATAAGTTATTCGTCTGATCTAATAAGTCTTTAATTGCTTTCACATCGTCCTCCGCAGAT 
GCTTGAAGCAGATCTTTCTTACCCTGATTCTGGTACTTGATAGAGATCTGCGCCAGATTGTCT 
TTGTTTTGAGCAATTTCGTCGAAGATCATCGGGATTGCCGCAAAGTTCGCCAGAATTTCCTCA 
AAACGACACTGTTTATCAATATCACGATGTTTATTAAATTCCTCAAGTGCCAGTTTGATAGTT 
TCTAAGCTCAGGTATTTAGCTTTTTCTGTTTTCTTTGCAATCAGTTCCTGTTCCTTCTTGGACG 
GGTTGTCCAGATTTTTCGGCGCGATTTGTTGGGTGATGTATTCCAAAACTGCCGTGCCGATCA 
CGCTATAGTCATCGAAAACTTGTTGACTGAGATCGGTCAGAGATTTGTCGTTTTTAAAGTAA 
ATCTTAGACAGATCTAGTTTCTGCGCTTTGAGGTCGTCAAAGAGCAGGGACAGAGTTTCTTT 
AATAGATTTCTCTTCCACGGTTTTGAACGCCGCAATCTGCTCATAAAAGCTCTGCATCGTGGT 
GACAACGTCGCTATCATCTTCCAGTTTATCAATTACGAAGGATTTAGATTCGGTGTCCGATA 
AAATCTGTTTAAACAGAACGGACATTTTATACTTTTTCAGGGTTTTGTCGTTGATTTGTTGGC 
TATACAGGTTAATGTATTCGTTGATGCCCTTACGCTTGGTGTTTTCGCCGTTAACAAATTTGC 
CACCAATAATGGTGTTGAATTTGGTGATGCCAGATTGATTCAGGTAATTGTTGAAATTAGCG 
ATTTCGAAAACCTCGTCCAGTGAGAAAACACGCTGGTTAACTTCGGAGGTTTTATAGTCGAT 
GTCGAAGGTCAGTTCTTCCGCCAGATCTTTCTTGATCTGTTCATAGTTAATAGCTTCCGGTGC 
TTTGTCTTTCAGAGATTCATATTTCGCTTTGTTTTCCAGAAACTTCGGCAGGTTGTCGTCCAC 
GATACGATAAATAATAGAGGTCGGAATATCGTTGCTCGAATATACATTCTTACGGTTTTCAT 
GAAAACCTTTGAAATACGTCGTCCAGCCTTTGAAAGACTTGATGATTTCGGTATTCGAATAT 
GACCTGATCAAAGATAAACGTTTCACCGAAGATAAGTTCTTTTTCCACTGTCCGATTACCATC 
AACTTCAAATCTAGCGGTGCGAACAAGTTCAACGATGAAATTAACTTATTACTGAAAGAGA 
AAGCTAATGACGTACACATCTTATCTATTGATCGCGGTGAACGTCATTTAGCATACTATACA 
CTGGTAGATGGTAAAGGTAATATTATTAAACAGGATACTTTCAATATTATCGGTAATGACCG 
TATGAAAACCAACTATCACGATAAGCTGGCGGCGATCGAAAAAGATCGTGATTCTGCGCGT 
AAAGATTGGAAGAAAATTAACAATATCAAAGAAATGAAAGAAGGCTATCTGAGCCAAGTGG 
TGCACGAGATCGCAAAACTGGTGATTGAATATAACGCTATCGTGGTTTTCGAAGATCTGAAC 
TTTGGTTTTAAACGTGGTCGCTTCAAAGTAGAAAAACAGGTGTACCAAAAACTGGAAAAAA 
TGCTGATTGAAAAACTGAACTATCTGGTTTTTAAAGACAACGAATTTGACAAAACGGGTGGC 
GTACTCCGTGCCTATCAGCTGACCGCTCCGTTCGAAACGTTCAAGAAAATGGGTAAACAAAC 
GGGGATTATCTATTATGTGCCAGCTGGTTTCACCTCCAAGATTTGTCCAGTTACGGGCTTCGT 
TAACCAGCTGTACCCGAAATACGAGAGCGTTAGCAAATCTCAAGAATTTTTCAGCAAATTCG 
ACAAGATCTGCTATAATCTGGATAAAGGCTATTTCGAGTTCAGCTTCGATTACAAAAACTTC 
GGCGATAAAGCGGCTAAAGGTAAGTGGACTATTGCTAGCTTTGGTAGCCGTCTGATTAACTT 
TCGCAACTCCGACAAAAACCATAATTGGGACACGCGTGAAGTGTATCCGACCAAAGAACTG 
GAAAAATTACTGAAAGACTATTCCGGACACTCAGAAGGGTTATAGGAATAGTCACTACTGG 
GGTAAGCACTTCGGAAATTATATTATTCTCGCTTCTTATTGCGGTAACGTGATCCTGAACGAT 
ACTTATTACTTTGTAATTTACTTAACGTCGGAGTCCCTGCAATCTTCTAGTACCCGCTTCCCG 
AATACAGGAGATAACTTTTTAACACTCAAGAGTTGCTTCGTGCTTAGCCAGTCTTGGATTTG 
ATTGCTCTAATCCTTCAACGTGTCAAAGACAGTGTATCTGGTCAAGTAAAGTCTAGAGAAAG 
GCGTAGTCAGTTACGGAGTTATCCCACCTTAGTGTTACTCCGATTTAATTTCTGCTTTCTTTG 
ATTTCTACCCGACTTTCGCCGTGACTTCAATAGAGAGGCAGGCTCTTGCTATTTCTTTCAAGG 
GCTTGTCCAACTACCTAATTAAGATAAAGATACGGCAGTTGACGCACTGCCGATAATTTCTT 
TACGTCAGCGAAATTAAATCGAGCACCAGTCGTAGAGTCGCGGTTGCCTAGCAGTTTATCTC 
GCGTACGGGCCTTCGCTACTTACACGATACCTAGTACGTGGATTCGGGTAGCACCAGAAGTC 
TATAGCATGTGCATACCTTTGGTCGAAAAAAAAAGCCCGCACTGTCAGGTGCGGGCTTTTTT 
CAGTGTTTCCTTGCCGGATTACGCCCCGCCCTGCCACTCATCGCAGTATTGTTGTAATTCATT 
AAGCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACTTGGATCGCCAGTGGC 
ATTAACACCTTGTCGCCTTGCGTATAATATTTTCCCATAGTGAAAACGGGGGCGAAGAAGTT 
GTCCATATTTGCTACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCACTGACGA 
AAAACATATTTTCGATAAAC 
gpJ VARIANT
1A2
(SEQ ID NO: 179)
ATGGGTAAAGGAAGCAGTAAGGGGCATACCCCGCGCGAAGCGAAGGACAACCTGAAGTCC 
ACGCAGTTGCTGAGTGTGATCGATGCCATCAGCGAAGGGCCGATTGAAGGTCCGGTGGATG 
GCTTAAAAAGCGTGCTGCTGAACAGTACGCCGGTGCTGGACACTGAGGGGAATACCAACAT 
ATCCGGTGTCACGGTGGTGTTCCGGGCTGGTGAGCAGGAGCAGACTCCGCCGGAGGGATTT 
GAATCCTCCGGCTCCGAGACGGTGCTGGGTACGGAAGTGAAATATGACACGCCGATCACCC 
GCACCATTACGTCTGCAAACATCGACCGTCTGCGCTTTACCTTCGGTGTACAGGCACTGGTG 
GAAACCACCTCAAAGGGTGACAGGAATCCGTCGGAAGTCCGCCTGCTGGTTCAGATACAAC 
GTAACGGTGGCTGGGTGACGGAAAAAGACATCACCATTAAGGGCAAAACCACCTCGCAGTA 
TCTGGCCTCGGTGGTGATGGGTAACCTGCCGCCGCGCCCGTTTAATATCCGGATGCGCAGGA 
TGACGCCGGACAGCACCACAGACCAGCTGCAGAACAAAACGCTCTGGTCGTCATACACTGA 
AATCATCGATGTGAAACAGTGCTACCCGAACACGGCACTGGTCGGCGTGCAGGTGGACTCG 
GAGCAGTTCGGCAGCCAGCAGGTGAGCCGTAATTATCATCTGCGCGGGCGTATTCTGCAGGT 
GCCGTCGAACTATAACCCGCAGACGCGGCAATACAGCGGTATCTGGGACGGAACGTTTAAA 
CCGGCATACAGCAACAACATGGCCTGGTGTCTGTGGGATATGCTGACCCATCCGCGCTACGG 
CATGGGGAAACGTCTTGGTGCGGCGGATGTGGATAAATGGGCGCTGTATGTCATCGGCCAGT 
ACTGCGACCAGTCAGTGCCGGACGGCTTTGGCGGCACGGAGCCGCGCATCACCTGTAATGC 
GTACCTGACCACACAGCGTAAGGCGTGGGATGTGCTCAGCGATTTCTGCTCGGCGATGCGCT 
GTATGCCGGTATGGAACGGGCAGACGCTGACGTTCGTGCAGGACCGACCGTCGGATAAGAC 
GTGGACCTATAACCGCAGTAATGTGGTGATGCCGGATGATGGCGCGCCGTTCCGCTACAGCT 
TCAGCGCCCTGAAGGACCGCCATAATGCCGTTGAGGTGAACTGGATTGACCCGAACAACGG 
CTGGGAGACGGCGACAGAGCTTGTTGAAGATACGCAGGCCATTGCCCGTTACGGTCGTAAT 
GTTACGAAGATGGATGCCTTTGGCTGTACCAGCCGGGGGCAGGCACACCGCGCCGGGCTGT 
GGCTGATTAAAACAGAACTGCTGGAAACGCAGACCGTGGATTTCAGCGTCGGCGCAGAAGG 
GCTTCGCCATGTACCGGGCGATGTTATTGAAATCTGCGATGATGACTATGCCGGTATCAGCA 
CCGGTGGTCGTGTGCTGGCGGTGAACAGCCAGACCCGGACGCTGACGCTCGACCGTGAAAT 
CACGCTGCCATCCTCCGGTACCGCGCTGATAAGCCTGGTTGACGGAAGTGGCAATCCGGTCA 
GCGTGGAGGTTCAGTCCGTCACCGACGGCGTGAAGGTAAAAGTGAGCCGTGTTCCTGACGG 
TGTTGCTGAATACAGCGTATGGGAGCTGAAGCTGCCGACGCTGCGCCAGCGACTGTTCCGCT 
GCGTGAGTATCCGTGAGAACGACGACGGCACGTATGCCATCACCGCCGTGCAGCATGTGCC 
GGAAAAAGAGGCCATCGTGGATAACGGGGCGCACTTTGACGGCGAACAGAGTGGCACGGTG 
AATGGTGTCACGCCGCCAGCGGTGCAGCACCTGACCGCAGAAGTCACTGCAGACAGCGGGG 
AATATCAGGTGCTGGCGCGATGGGACACACCGAAGGTGGTGAAGGGCGTGAGTTTCCTGCT 
CCGTCTGACCGTAACAGCGGACGACGGCAGTGAGCGGCTGGTCAGCACGGCCCGGACGACG 
GAAACCACATACCGCTTCACGCAACTGGCGCTGGGGAACTACAGGCTGACAGTCCGGGCGG 
TAAATGCGTGGGGGCAGCAGGGCGATCCGGCGTCGGTATCGTTCCGGATTGCCGCACCGGC 
AGCACCGTCGAGGATTGAGCTGACGCCGGGCTATTTTCAGATAACCGCCACGCCGCATCTTG 
CCGTTTATGACCCGACGGTACAGTTTGAGTTCTGGTTCTCGGAAAAGCAGATTGCGGATATC 
AGACAGGTTGAAACCAGCACGCGTTATCTTGGTACGGCGCTGTACTGGATAGCCGCCAGTAT 
CAATATCAAACCGGGCCATGATTATTACTTTTATATCCGCAGTGTGAACACCGTTGGCAAAT 
CGGCATTCGTGGAGGCCGTCGGTCGGGCGAGCGATGATGCGGAAGGTTACCTGGATTTTTTC 
AAAGGCAAGATAACCGAATCCCATCTCGGCAAGGAGCTGCTGGAAAAAGTCGAGCTGACGG 
AGGATAACGCCAGCAGACTGGAGGAGTTTTCGAAAGAGTGGAAGGATGCCAGTGATAAGTG 
GAATGCCATGTGGGCTGTCAAAATTGAGCAGACCAAAGACGGCAAACATTATGTCGCGGGT 
ATTGGCCTCAGCATGGAGGACACGGAGGAAGGCAAACTGAGCCAGTTTCTGGTTGCCGCCA 
ATCGTATCGCATTTATTGACCCGGCAAACGGGAATGAAACGCCGATGTTTGTGGCGCAGGGC 
AACCAGATATTCATGAACGACGTGTTCCTGAAGCGCCTGACGGCCCCCACCATTACCAGCGG 
CGGCAATCCTCCGGCCTTTTCCCTGACACCGGACGGAAAGCTGACCGCTAAAAATGCGGATA 
TCAGCGGTAACGTGAATGCGAACTCCGGGACGCTCAACAACGTCACGATTAACGAGAACTG 
TCGGGTTCTGGGAAAATTGTCCGCGAACCAGATTGAAGGCGATCTCGTTAAAACAGTGGGC 
AAAGCTTTCCCCCGGGACTCCCGTGCACCGGAGCGGTGGCCATCAGGAACCATTACCGTCAG 
GGTTTATGACGATCAGCCGTTTGACCGGCAGATTGTTATTCCGGCGGTGGCATTCAGCGGCG 
CTAAACATGAGAAAGAGCATACTGATATTTACTCCTCATGCCGTCTGATAGTGCGGAAAAAC 
GGTGCTGAAATTTATAACCGTACCGCGCTGGATAATACGCTGATTTACAGTGGCGTTATTGA 
TATGCCTGCCGGTCACGGTCACATGACACTGGAGTTTTCGGTGTCAGCATGGCTGGTAAATA 
ACTGGTATCCCACAGCAAGTATCAGCGATTTGCTGGTTGTGGTGATGAAGAAAGCCACTGCA 
GGCATCACGATTAGCTGA 
STFs
>WT STF
(SEQ ID NO: 180)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGT
AATGGATGAGACTAATCGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACA
GCACCAACCGCGCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGG
CCGCGATTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCC
GCAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTAAACA
ACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAATAAATTACCG
TATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTTGGCAGGGATATTCT
GGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCCGGTGAGAATTCGGCCTTTC
CGGCAGGTGCGCCGATCCCGTGGCCATCAGATATCGTTCCGTCTGGCTACGTCCTGATGCAG
GGGCAGGCGTTTGACAAATCAGCCTACCCAAAACTTGCTGTCGCGTATCCATCGGGTGTGCT
TCCTGATATGCGAGGCTGGACAATCAAGGGGAAACCCGCCAGCGGTCGTGCTGTATTGTCTC
AGGAACAGGATGGAATTAAGTCGCACACCCACAGTGCCAGTGCATCCGGTACGGATTTGGG
GACGAAAACCACATCGTCGTTTGATTACGGGACGAAAACAACAGGCAGTTTCGATTACGGC
ACCAAATCGACGAATAACACGGGGGCTCATGCTCACAGTCTGAGCGGTTCAACAGGGGCCG
CGGGTGCTCATGCCCACACAAGTGGTTTAAGGATGAACAGTTCTGGCTGGAGTCAGTATGGA
ACAGCAACCATTACAGGAAGTTTATCCACAGTTAAAGGAACCAGCACACAGGGTATTGCTT
ATTTATCGAAAACGGACAGTCAGGGCAGCCACAGTCACTCATTGTCCGGTACAGCCGTGAGT
GCCGGTGCACATGCGCATACAGTTGGTATTGGTGCGCACCAGCATCCGGTTGTTATCGGTGC
TCATGCCCATTCTTTCAGTATTGGTTCACACGGACACACCATCACCGTTAACGCTGCGGGTA
ACGCGGAAAACACCGTCAAAAACATTGCATTTAACTATATTGTGAGGCTTGCATAA
>WT STF accessory protein 1
(SEQ ID NO: 181)
ATGGCATTCAGAATGAGTGAACAACCACGGACCATAAAAATTTATAATCTGCTGGCCGGAA 
CTAATGAATTTATTGGTGAAGGTGACGCATATATTCCGCCTCATACCGGTCTGCCTGCAAAC 
AGTACCGATATTGCACCGCCAGATATTCCGGCTGGCTTTGTGGCTGTTTTCAACAGTGATGA 
GGCATCGTGGCATCTCGTTGAAGACCATCGGGGTAAAACCGTCTATGACGTGGCTTCCGGCG 
ACGCGTTATTTATTTCTGAACTCGGTCCGTTACCGGAAAATTTTACCTGGTTATCGCCGGGAG 
GGGAATATCAGAAGTGGAACGGCACAGCCTGGGTGAAGGATACGGAAGCAGAAAAACTGT 
TCCGGATCCGGGAGGCGGAAGAAACAAAAAAAAGCCTGATGCAGGTAGCCAGTGAGCATAT 
TGCGCCGCTTCAGGATGCTGCAGATCTGGAAATTGCAACGAAGGAAGAAACCTCGTTGCTG 
GAAGCCTGGAAGAAGTATCGGGTGTTGCTGAACCGTGTTGATACATCAACTGCACCTGATAT 
TGAGTGGCCTGCTGTCCCTGTTATGGAGTAA 
>SIED6
(SEQ ID NO: 182)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT
ATAGCTGATCCTGCTTCTGTCCCTCCGCTTCCTGATATCTGGCTACCCTTGAATGATTCTCTG
GAAGCGATAACAGGGTATGCGCCGGGGTATAAAACAATAACCATCGGCAGCGATGAAATCA
CTGTGCCAGTTAATGGCATATGCCAATTTAGCCGGGCTTCATCTGCAACGTATATTGATAAG
TCCGGGCATATTACCGTGGCAGGGAATAACGTTCCTCGTTTTGAAAAATATGGTTTGCTGAT
AGAGAATCAGCGAACAAACATGTTCGTAAATAGTTTTAATCCTGATGCGTGGAATAAAAGC
GGTGGTATATCTGTAACATCATCAACAGATGAATTTGAGTTTAAATATGGACGTTTCACAGT
AGGAAGCGACATAGCAGGAACGACAACAGGGAGAAATATATGCACAGTTGCTGGTAATAG
AGGCATAGATGTGACTGGCGATGATCAGTACAGTAAAGGTCCGTATGTTACCGCGTCGTTCA
GGGTAAGAAGTGATCTCAATGTTCGCGCACGTATCCGTTTTGAACGGTATAACTCGGAAGGA
TACACTTTCCTTTGTGACGCCTATTTGTCATTACAGACCCATGAACTACAAATTACGGGTGAT
AATGCCCAGCTATTAACAGCAAACTTTGAAATCGATCCAGGTAGTGGATGGATATATTTTCA
GGCAACCCTGAAATGTCTGCCAGAATGGGGAATGGTTGGTACGCAGTTGCAAATTGCAGCC
GACAGAGCTGTGGGGTCTTTTGCAACAGGTGACTGGATAGAAGTAACCACCCCGCAATTTGA
GTATGGTGCTTGTGCAACTTCCTTTATCATAACGACAACAGAGCCAGCGACTCGTGCATCAG
ATTTATGTAAATTTCCGCTGATGAAAAATATGTATACCATGCCTTTTACGTTCATGGTGGAAG
TCCATAAAAACTGGTTTATTGCTCATAATGCTGCACCGCGAGTAATTGATACAGAAAACCAT
CAGTCAGGTGCTCCATTTATCATGGGATTTGGCTCTTCTGGAACTATCAGTCAGGACGGTTAT
CCCTATTGTGATATAGGCGGGGCTAACCGACGTGTATATGAGTCATGCGGAGTAAGAGATCT
TGTTATGGGATTCAGGGTTAAGGCTGACGGCATGACATGCTCATTTGCAAATAAGCATATAA
GCACAGAAACAAAAACAGTATGGAAATATATTCGTGAAGCTGCTGTGATTCGTATCGGGGG
ACAAACGACGACAGGATTACGACACCTTAATGGTCATATAAAAAACCTCCGTTTCTGGAACA
GAGCATTGTCAGATACGCAGCTTAAGGAATACGTATAA
>SIED6 accessory protein 1
(SEQ ID NO: 183)
ATGCGGGATATAACATTACGATTCGATAACAGAGAACAGTTTAACGCAATTGTATATGACAG 
TGGCCTGTTCAGTCTTGAAGAAGAAAACGGGATTCTTGTTGATGTTATTGGCCGCGTTATCG 
ATTACGAGGAGCCAGAAAACGAAAGATGTACAGGCATTGATCGCGGCGGTTTTTTCGTAAA 
CATGAGGATTGTTGATAGCAGTAAAAACATATCTTCTTTAATGCCTTTCATTACGACAGATC 
AGCATGTAAGGACATGGGCTTAA 
>SIED6 accessory protein 2
(SEQ ID NO: 184)
ATGGTTACAAAAACAGTAATTCCTGATGACATCAAAACGCTAAAATCCGATGTTAGTAAACT 
AAAAAACGATCAAGGAAGCTACGCAACAAAATCATATGTAGACAGCAAAGATGAAACCGTT 
GGTGACTGGTCTGCTTCATGGTATCAGCAGGTATTGCCAACTAGCGGAGCTATATTTGGGAG 
AAAACTCCGCTCAACTCACCGGACGGCAGGTGTTGAGGATGCGTATTGCGAACTATACCTTA 
AAAAATGGATAGACAGCCCAGGGAACGCAATGGCGCGCCTTAACCTGAACGATAACGGTGA 
AAATATTTGCTGGGATTTTACCAACCTTTACGGCGGAACAATGATCTTCCCTGGAACTTCAG 
GCTATCTGAAAATGGGGAACTGTCTCATGTCGTATGGTGTGCGGGGAAGTAACGCGCTTATT 
AAGTTTGATAATACAGACTCATTGCAGATCAAATATGCTAATCACGGGTCGACCATGACACT 
AAACACGCAAGGCACGGCGTATTCTGGTGTGTCGACGTTATTATGGGGAAATTCCAGTCGTC 
CAGTTGTTTATGAGATTAGGGATGATGGCGGGCTTTTTTTGTTTTATGCACAAAGGAACCCA 
GATAAAACCTATCAGCTTGAGATAAACGGGCCATGTAAGGCTACATCATTCGACCAGGTGTC 
GGACAGAGATCTTAAAGAAAACATTCGGGTTATTGATAATGCCACTGAACGCATCAGATTA 
ATGAATGGGTATACTTACCGTCTCAAGTCTAATGGTATGCCTTATGCTGGCGTTATTGCGCAA 
GAGGCACTTAATGCAATCCCTGAATCAGTTGGTAGCACAATAAAGTACAAGAGCGGGGACA 
ATGGGTCTGATGGAGAATAG 
SIEA11
(SEQ ID NO: 185)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGCAGC
AAATGACAACGCAAATTCACGTCTGGCGAAAAATCAGAATGGTGCAGATATCCAGGATAAA
TCAGCTTTTCTGGACAATGTTGGCGTTACCAGCCTGACGTTTATGAAAAACAATGGCGAAAT
GCCGGTTGATGCTGATCTGAATACGTTTGGTTCTGTTAAGGCTTATTCAGGTATCTGGTCTAA
AGCAACGTCCACCAACGCAACACTGGAGAAAAACTTCCCTGAAGATAATGCTGTCGGTGTG
CTTGAGGTTTTTACTGGCGGCAATTTTGCAGGCACGCAACGCTATACCACACGTGACGGAAA
TTTGTATATCCGCAAACTCATTGGAACATGGAATGGTAATGATGGACCATGGGGAGCATGGC
GCCATGTTCAGGCTGTAACGCGAGCTCTAAGTACGACCATTGACCTTAACTCTCTCGGTGGC
GCAGAACATTTAGGTCTATGGAGAAACAGCAGTTCAGCAATAGCTTCTTTTGAACGACATTA
CCCCGAGCAGGGAGGAGACGCGCAGGGCATTCTGGAAATTTTCGAAGGTGGGCTATATGGA
CGCACACAGCGTTATACAACCCGTAACGGGACTATGTATATTCGCGGCCTGACAGCCAAATG
GGATGCAGAAAATCCACAGTGGGAAGACTGGAACCAAATTGGTTATCAGACCAGTAGTACC
TTCTATGAGGATGACCTGGATGATTTGATGTCTCCAGGTATTTACAGTGTGACAGGCAAAGC
GACCCACACCCCAATCCAGGGGCAGTCTGGTTTTCTGGAAGTCATCAGGCGCAAGGATGGTG
TCTATGTTTTGCAACGTTACACGACCACAGGAACCAGCGCAGCTACAAAAGACCGTTTATAT
GAGCGAGTGTTTCTTGGTGGCTCATTTAACGCGTGGGGGGAGTGGCGACAGATTTATAACTC 
AAACTCTTTGCCGTTAGAGTTGGGTATCGGTGGCGCAGTGGCAAAACTCACCAGCCTGGACT 
GGCAGACATACGATTTTGTGCCGGGCAGTCTGATAACCGTTCGGCTGGATAACATGACCAAT 
ATTCCCGACGGTATGGACTGGGGCGTCATTGATGGCAACCTGATAAACATCTCAGTCGGTCC 
GAGTGATGATTCTGGTTCGGGACGCTCAATGCATGTATGGCGCAGCACTGTAAGTAAAGCCA 
ACTACCGCTTTTTTATGGTGCGTATTTCAGGAAATCCGGGAAGCCGCACGATCACGACAAGA 
CGTGTGCCAATTATCGACGAAGCCCAGACATGGGGCGCGAAACAGACATTCAGTGCTGGCC 
TTTCTGGTGAACTGTCCGGCAATGCGGCGACAGCAACAAAGCTGAAAACAGCCCGTAAAAT 
TAATAACGTTTCGTTTGATGGAACATCAGATATTAACCTGACGCCGAAAAATATTGGTGCAT 
TTGCTTCAGGAAAAACAGGAGACACCGTTGCGAATGATAAAGCCGTTGGATGGAACTGGAG 
TAGCGGAGCCTATAACGCAACTATTGGTGGGGCATCAACGTTAATTCTTCATTTTAATATCG 
GGGAAGGAAGTTGTCCCGCCGCCCAGTTTCGCGTTAATTATAAGAACGGTGGTATTTTTTAT 
CGTTCTGCTCGTGACGGTTACGGATTCGAGGCTGACTGGTCTGAGTTTTATACCACAACGCG 
AAAACCTACAGCGGGAGATGTCGGTGCACTGCCGTTATCTGGTGGTCAATTGAATGGTGCTC 
TGGGTATAGGAACATCCAGTGCTCTTGGCGGTAATTCGATTGTTTTGGGTGATAATGACACG 
GGCTTTAAACAAAATGGTGATGGTAATCTGGATGTTTATGCTAATAGCGTCCATGTTATGCG 
CTTTGTCTCCGGAAGCGTTCAAAGTAATAAAACCATAAATATTACGGGGCGTGTTAATCCCT 
CGGATTACGGTAACTTTGATTCCCGCTATGTGAGAGATGTCAGACTTGGCACACGTGTTGTC 
CAGACCATGCAGAAAGGGGTGATGTATGAGAAAGCAGGGCACGTAATTACCGGGCTTGGTA 
TTGTCGGTGAAGTCGATGGTGATGACCCCGCAGTATTCAGACCAATACAAAAATACATCAAT 
GGCACATGGTATAACGTCGCACAGGTGTAA 
SIEA11 accessory protein 1
(SEQ ID NO: 186)
ATGCAGCATTTAAAAAATATTACTGCGGGTAATCCAAAAACTGTTGCCCAATATCAACTGAC 
AAAAAATTTTGATGTTATCTGGTTATGGTCCGAAGAGGGAAAAAACTGGTATGAGGAAGTA 
AGTAATTTTCAGGAAGACACGATAAAGATTGTTTACGATGAGAATAATATAATTGTCGGCAT 
CACCAGAGATGCTTCAACGCTCAACCCTGAAGGTTTTAGCGTTGTCGAGGTTCCTGATATTA 
CCGCCAACCGACGTGCTGATGACTCAGGTAAATGGATGTTTAAGGATGGTGCCGTGATTAAG 
CGGATTTATACGGCAGACGAACAGCTGCAACTGGCGGAATTACAGAAGTCAGCTTTGCTTTC 
CGAAGCTGAAACTATCATTCAGCCACTGGAACGCTCTGTCAGACTGAATATGGCAACAGATG 
AGGAGCGTAGCCGACTGGAAGCATGGGAACGCTACAGTGTTCTGGTCAGCCGTGTGGATCC 
TGCAAATCCTGAATGGCCGGAAATGCCGCAATAA 
EB6
(SEQ ID NO: 187)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA 
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA 
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC 
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA 
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC 
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG 
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC 
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC 
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA 
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA 
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC 
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA 
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG 
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC 
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC 
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC 
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT 
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA 
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGATTGC 
GATGGATAATGCCAATGCCCGTCTGGCAAAAGACCGGAACGGAGCAGATATTCCCAATAAG 
CCGCTGTTTATCCAAAACCTCGGTTTACAGGAAACGGTAAACAAGGCTGGTAACGCCGTTCA 
AAAGACAGGCGATACCTTGTCCGGCGGACTTACTTTTGAAAACGACTCAATCCTTGCCTGGA 
TTCGGAATACTGACTGGGCAAAGATTGGATTTAAAAATGATGCCGACAGCGACACTGATTCA 
TACATGTGGTTTGAAACAGGCGACAACGGCAATGAATATTTCAAATGGAGAAGCCGCCAGA 
GCACCACAACAAAAGACCTGATGAATCTTAAATGGGATGCTTTGTATGTTCTTGTCAATGCC 
ATTGTAAATGGCGAAGTCATATCAAAATCAGCAAACGGCCTACGTATTGCTTATGGTAATTA 
CGGATTCTTTATTCGTAATGATGGTTCAAATACATACTTCATGTTGACAAACTCCGGTGACAA 
CATGGGGACTTATAACGGATTAAGGCCATTATGGATTAATAACGCTACTGGCGCTGTTTCGA 
TGGGGCGTGGTCTTAATGTTTCAGGGGAGACACTTTCAGACCGTTTTGCTATTAACAGCAGT 
AATGGTATGTGGATTCAGATGCGCGATAACAACGCTATCTTTGGGAAAAATATAGTTAACAC 
TGATAGCGCTCAGGCGTTACTTCGCCAGAATCACGCCGACCGAAAGTTCATGATAGGTGGAC 
TGGGGAACAAGCAATTTGGCATCTACATGATTAATAACTCAAGGACAGCCAATGGCACCGA 
TGGTCAGGCGTACATGGATAATAACGGTAACTGGCTTTGTGGTGCGCAAGTTATTCCCGGCA 
ATTATGGCAATTTTGACTCACGCTATGTGAGAGATGTCCGACTTGGCACACGTGTTGTTCAAT 
TGATGGCGCGTGGTGGTCGTTATGAAAAAGCCGGACACGCAATTACCGGATTAAGAATCATT 
GGTGAAGTAGATGGCGATGATGAAGCCATCTTCAGGCCAATACAAAAATACATCAATGGCA 
CATGGTATAACGTCGCACAGGTGTAA 
EB6 accessory protein 1
(SEQ ID NO: 188)
ATGCAGCATTTAAAAAATATTAAGTCTGGAAATCCTAAAACGAAAGAACAATATCAGCTAA 
CAAAGAATTTTGATGTTATCTGGTTATGGTCCGAAGACGGTAAAAACTGGTATGAAGAAGTA 
AATAACTTTCAGGACGACACCATAAAGATTGTATACGACGAAAATAATATTATTGTTGCCAT 
AACCAAAGATGCCTCAACGCTTAATCCCGAAGGCTTTAGCGTCGTTGAGATTCCAGATATAA 
CAGCCAATCGTCGTGCCGATGATTCAGGGAAGTGGATGTTTAAGGACGGAGCTGTGGTTAA 
ACGGATTTATACGGCAGACGAGCAACAACAACAGGCCGAATCACAAAAGGCCGCGTTACTT 
TCCGAAGCAGAAAACGTTATTCAGCCACTGGAACGCGCTGTCAGACTGAATATGGCGACGG 
ATGAGGAACGCGCACGACTGGAGTCATGGGAACGCTACAGTGTTCTGGTCAGCCGTGTGGA 
TACGGCAAAGCCAGAATGGCCACAAAAGCCTGAATAA 
AH11L
(SEQ ID NO: 189)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT 
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA 
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGCAGC 
AAATGACAACGCAAATTCACGTCTGGCGAAAAATCAGAACGGTGCAGATATCCAGGATAAA 
TCAGTTTTTCTGGACAATGTTGGCGTTACCAGCCTGACGTTTATGAAAAACAATGGCGAAAT 
GCCGCTTGATGCTGATCTGAATACATTTGGTCCCGTTAAGGCTTATCTGGGGATCTGGTCTAA 
AGCTACCTCAACTAACGCAACACTGGAGAAAAATTTCCCGGAAGATAATGCTGTCGGTGTGC 
TTGAGGTTTTTGCTGCCGGCAATTTTGCAGGTACGCAACGCTTTACCACAAGAGACGGCAAT 
GTATACATGCGTAAACTCGCCAATAAGTGGAATGGCACTGATGGTCCGTGGGGCGTATGGC 
GTCACACTCAATCAGCTACCCGCCCTTTGAGTACGACTATAGACCTGAATACGCTTGGAGCC 
GCCGAACATCTTGGTTTATGGCGTAACAGTAGCTCGGCTATAGCTTCATATGAACGCAATTA 
TCCAGAGGAAGGCGGCTTTGCTCAGGGGACGCTTGAGATCCTCGAAGGCGGGAATTATGGA 
AGAACGCAACGTTATACCACTCGCCGTGGAAATATGTATGTCCGCTGCCTTGCGGCAAGCTG 
GGATGCATCAAATCCGCAGTGGGAACCGTGGTTAAGAGTCGGTCATCAGTCAGAGAGTCGT 
TATTACGAAGGTGATTTGAATGATGTAACCTCACCAGGTATTTACAGCGTTACAGGTAAAGC 
GACCAACGGTCCAGTACTGGACGGAAACGGCGTGACTGTACTCGGCATTCTGGAAGTGTTG 
AGGCGGTTTGATGGTGTTAATGTATGGCAGCGTTATACAACTGCCGGAACAGGTACAACCCT 
TAAAGGCCGCACCTTTGAGCGCGTCTTTACCGGCAGCTCATGGAGCGAATGGCGGGAAGTCT 
ACACCTCGTATTCACTTCCCCTGAATCTGGGTATCGGCGGTGCTGTGGCAAAGCTCACCAGC 
CTGGACTGGCAGACCTACGATTTTGTGCCGGGCAGTCTGATAACCGTTAGGCTGGATAATAT 
GACCAATATTCCCGACGGTATGGACTGGGGCGTCATTGATGGCAACCTGATAAACATCGCAG 
TTGGTCCGAGTGATGATTCCGGTACGGGGCGCTCAATGCATGTATGGCGCAGCACTGTAAGT 
AAAGCGAACTACCGATTTTTTATGGTGCGTATTTCAGGAAATCCGGGAAGCCGCACGATCAC 
AGCAAGACGAGTACCAATCATTGACGAAGCCCAGACATGGGGCGCGAAACAGACATTCAGT 
GCTGGCCTTTCTGGTGAACTGTCCGGCAATGCGGCGACAGCAACAAAGCTGAAAACAGCCC 
GTAAAATTAATAACGTTTCGTTTGATGGAACATCAGATATTAACCTGACGCCGAAAAATATT 
GGTGCATTTGCTTCAGGAAAAACAGGAGACACCGTTGCGAATGATAAAGCCGTTGGGTGGA 
ACTGGAGTAGCGGAGCCTATAACGCAACTACTGGTGGGGCATCAACGTTAATTCTTCATTTT 
AATATCGGTGAAGGAAGTTGTCCCGCCGCCCAGTTCCGCGTTAATTATAAGAACGGCGGTAT 
TTTTTATCGTTCTGCTCGTGACGGTTACGGATTCGAGGCTGACTGGTCTGAGTTTTATACCAC 
AACGCGAAAACCTACAGCGGGAGATGTCGGTGCACTGCCGTTATCTGGTGGTCAATTGAATG 
GTGCTCTGGGTATAGGAACATCCAGTGCTCTTGGCGGTAATTCGATTGTTTTGGGTGATAAT 
GACACGGGCTTTAAACAAAATGGTGATGGTAATCTGGATGTTTATGCTAATAGCGTCCATAT 
TATGCGCTTTGTCTCGGGAAGTATTCAAAGTAATAAAACCATAAATATTACGGGGCGTGTTA 
ATCCCTCGGATTACGGTAACTTTGATTCCCGCTATGTCCGGGATATCCGGCTTGGTGGTGCTG 
CCACATACAAACCTGCGAACAATGGCATGACATGGACACATCAGGCACCGTCCGGGTGTGT 
ATATTCCGGCATTATTGTTCAGGATACCGGCTCAAACTCTGCCGATAACATTGGTGGTGTAT 
ATTACAGGCCGGTTCAGAAATACATTAACGGGACATGGTATAACGTGGCGCAGGTATAA 
AH11L accessory protein 1
(SEQ ID NO: 190)
ATGCAGCATTTGAAAAATATTACGGCGGGTAATCCAAAAACGGTTGAACAATATCAATTGA 
CAAAGGGTTTTGATGTTGTCTGGTTTTTTTCAGAAGATGGTAAGAACTGGTACGAAGAACAA 
AAGTATTTTGCTGATGACACGATAAAAATAGCGTACGACAAAGATAATATTATCCGCTATGT 
GGAAAAGGATGTGACAGCTATCAGACCGGATGGATTAAGTGTTGTTGAAGTGGCGGATATT 
ACTGCTAACCGACGGGCGGACATTTCAGGGGGCTGGATGTTTAAGGACGGCAAAGTGATTA 
AACGCATTTATACGGCAGAGGAATTGCTGCAGCAGGCAGAAAACCGGAAAGCCAGACTTCT 
TGCAGATGCTGAATCCGTGATTTTGCCGCTGGAGCGCGCGGTCAGACTGAACATGGCAACAG 
ATGAGGAGCGTAGCCGACTGGATGCATGGGAGCGTTACAGCGTTCTGGTCAGTCGTGTGGAT 
CCTGCAAATCCTGAATGGCCGGAAATGCCGCAATAA 
WW55 3.0 accessory protein 1
(SEQ ID NO: 191)
ATGGCAATATCTTCTGGATGGGTAGGATCATCTGCTGTGTCCGAGACTGGTCAACGGTGGAT
GAGCGCCGCAATGCAAGCTGTTCGCTTAGGTCGTCCGGCGTATATGTCGGCAATGGTCGGAC
GCTCTAAAGAGATTCATTATAGCATTGGTGCTAGTAACTCTTACAATAAAGACACTCTTATT
AACTGGATGAAAGCACAAGGATCTACTCCGGTAGTAATTACTATCACGGGTAATATTGTTTC
CCAATCTACTGGCGTTCCTTGTCTTGATTTCCCTAGCTCACTGACAAACGAATATGTAACACT
CATTATTAACTCTGGTGTTCATGTATTAGGTCGTGGAGGAAATGGCGGAAGTAACTCTGCTG
GTGGAGCAGGAGGAAATGCAATAAATAACGGAATTGGAACTCGTTTAAGAATAAACAATAA
TGGTATTATTGGTGGTGGCGGTGGTGGCGGTGCTGGTGCTAGATACAATCCTTTCCCTCAAA
TGGATATGAAATTTGGCGGCGGTGGAGGCCGTCCATTTGGTGCTGCGGGTGCGGCAGGAGG
CGGCGCAGCGGCAGCATCTGCTGGTACAATTTCTGCCCCAGGTAAAGGCACTGTTTCTGGGG
TTCATTATGGAGGAGATGGTGGAGATTTGGGAGCTGCTGGCAAATCTTCATATATTAAAGGT
GGTACTGGTGGAACTGTTCACTCGGGTGGTGCTGCGGGTAAAGCTGTTACTGGTAATGCCCC
TCGCTGGGATAAAGTAGGCACGATCTACGGTGCTCGCGTGTAA
WW55 3.0 accessory protein 2
(SEQ ID NO: 192)
ATGTCCAATCAGCATGAACAAATGATTAATGTCCTGAAAGTACGTCTGTTTGACACTCAAGA 
AAAGGCCGCATTCTTAGAAGGCCAACTGAAAGATCGTGAGCGTGTATTGATGGAACTGGTA 
CGCATTCTGGGTATTCAGCCAGACGAAAACGGCACTGTTTCCCTTGATGCTATTGTCGAAGA 
AGTGAAAGCACTTCTCCCTAAAGACGAAGCAGCGGAAGACGCAGAAGAGGAAGTAGAACT 
GATCACGGAGGCTTGA 
STF68B
(SEQ ID NO: 193)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGCTTCTGCCACTGCATCTGCCAACAGTCAA
AAAGCTGCAAAGACGAGCGAAACCAACGCAAAGACAAGCGAGACTGCGGCGGCTAACTCG
GCGAAAGCATCAGCTGCAAGCCAGACGGCTGCAAAAGCGAGTGAAGACGCAGCCAGAGAG
TATGCAAGCCAGGCTGCGGAGCCGTATAAACAAGTTTTGCAGCCGCTTCCCGATGTGTGGAT
ACCGTTTAACGATTCACTGGAAATGATTACTGGTTTCGCTCCTGGTTATAAAAAAGTAACTA
TCGGTGATGATGTTATTACTTTTCCATCAGAGAAGGTTGTATCTTTCACTCGCTCCACTTCTG
CAACGTATATAAACAAATCAGGTTCATTTGCTTTTGCAGAAATTAACGAGCCGCGCTTTGAA
AAGGAAGGTTTATTAATTGAAGGTCAGAGGACAAATACATTTACTAATAGTAACAATCCTTC 
ATTATGGAATTATGACGACAAGAATATAGAAATAACCACATCGGTTGATGAATATGGTTTTA 
AATATGGTTTGTTCGATGTAAAGGAAACATCAACTACTGAAAGGGCGACGATAATATCTACT 
GGATACAGTAGGGTTATTGATGTTGCTGCAAATGAATCTGTTACTTTGTCCTGTAGGGTTAA 
GAAGATAAATGGAGAAGGTATTATAACGTTAAGACCCAGAATATCTTTCGTTAACGATGAC 
GGTACAAGCAACACGCTGGTAGCTGGTTCCTACATAGATTGCGAAACTGGTGATGTTTTAGG 
TTTTTCTGGTGGGGATGCTGTAAATCATGTCATATACAGAGAAGCTAACGGATGGTTACGCG 
TCGAATTTACATATAAATCACCAGAAGCAAAAAGCATGTATGGGCGCTTTGAAATGGGAGC 
AGATAAAAGGGCGATCAAAAAAGGCGATCAGATAATGTTTACTACGCCGCAATTTGAAAAA 
GGATCGTGTGCATCATCATTTATCGTTACATCAGATGTGGCAGTTACACGGGCTAGTGACGT 
GGTAATAATGCCAATAAGACTGAACTGGTCAACACCTCCGTTAAGCGTTCTTATGGAAGTTA 
ATATCAACTGGGACAAAATGCCAAACAGTGAAGGTTCAGCAAGGCTTCTTAACGTGTCAAT 
AACTGGCGCAACAACGGATGTTGCTGATGAAAGTTATATGTATTTTGGTTTTACCTCTGGAG 
GCGCGCGCTCAATTATAACTAACGGAAAAGGAACAAAGACCGAGTATAAAGCCTACTGTAA 
CAGGACAACCCGCAGGTTTATTGCTGGGTTTAAGTTTACAGAGCAGAAAGAATTGCGTGCTG 
TTATAAACGGTAACTTTGGCGCTGTTGATGTATCACAACACACAAGACAACGTTATACAGAA 
GGGCCAATAAATATAGGCGGTCAATCAATATCAGGTAACAGGCATTTATTTGGACACGTGCG 
CAATTTACGTATCTGGCATAAGGAACTGACAGATGCACAAATGGGAGAAAGAATATAA 
STF68B accessory protein 1
(SEQ ID NO: 194)
ATGCGAGACTTAACCCTCAAATTCATAAACAAGGCCGACTTTTCGGCCTTTATGGATAGCAT 
TGGTTATGAAGATGACGAGGTAATGCAGAACAATGTTCTCATTGATGTGATAGGTAACGTGT 
ACAAAGAAACCGGAGAACTTACTGAAGATGGCGAGCCGGTATGTGTTAAGGAAGACGGATA 
TTTTGTAAACGTGCGCATCATTAATGATGCAAAAAAATCGTCAATATTCGATAAATACGCGG 
TTGTTGTTGAGCATCAACTTCGTGGCTGGATGTGA 
STF68B accessory protein 2
(SEQ ID NO: 195)
ATGGCTACATCGACAGTAATTCCTGATGACATCAAAACGCTAAAATCCGACGTTAGCAAATT
AAAAAACGATCAAGGAAGCTACGCAACAAAATCATATGTAGACAGCAAAGATGAAACCGTT
GGTGACTGGTCTGCTTCATGGTATCAGCAAGTATTGCCAACTAGCGGAGCTATATTTGGGAG
AAAACTCCGCTCAACTCACAGGACGGCAGGTGTTGAGGATGCGTATTGCGAACTATACCTCA
AAAAATGGATAGACAGTCCAGGTAACGCAATGGCGCGCCTTAACCTGAACGATAACGGGAC
AAACATTTGCTGGGACTTTACCAACCTTTATGGCGGTACGATGATTTTTCCCGGTGACAGCG
GATACCTCAAAATGGGTAACTGCCTTATGTCATACAGCAAGCGTGGAAGTAACGCGCTTATT
AAATTTGATTACACCGACACATTACAGATCAAATATGCTAATCATGGGTCAACCATGACATT
AAACACACAGGGAACCGCTCACGCTGGCGTAACAACTAGACTATGGGGTAATTCTAGCCGT
CCGGTTGTTTATGAAGTTGGCGTAGATGAGGCTCTGTATATGTTCTACGCACAGAAAACTAC
CAGCAATACCTACGAATTAACGGTTAACGGCGCGTGCAATGCAAGTGCATTTAATCAAGGCT
CTGACCGGGATCTGAAAGACAATATTCAGGTGATCGATAATGCAACCGACCGCATTCGTAA
AATGAACGGCTATACATACACGCTTAAAGAAAACGGTATGCCTTACGCTGGTGTTATTGCAC
AAGAAACCCTGGAAGCCATCCCCGAAGCCGTAGGGGCTATGATGAAATATCCAGACGGCGG
GAGTGGATTAGATGGAGAAGAAGGTGAACGGTATTACACTGTAGATTATTCTGGTGTTACTG
GCTTGCTTGTTCAGGTAGCCAGAGAGTCAGACGACAGGATAACAGCACTGGAAGAAGAAAA
CGCAGAATTAAGACAAAGATTATCTGCAATTGAGGCGGCGCTTGCGTCTAAATAA
>STF90B
(SEQ ID NO: 196)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGT
AATGGATGAGACTAATCGTAAATATACCGCACAGGACGCCACCACCGCGCGAAAAGGCCTT
GTCCAGCTAAGTAGCGTCACCAACAGCGATTCTGAAACGCTTGCGGCAACGCCAAAGGCGG
TTAAGACAGCGTATGACCTTGCTAACGGGAAATACACTGCACAGGATGCCACCACAGCGCG
AAAAGGTCTTGTCCAGCTCAGTAGCGCCACCAACAGCGATTCTGAAACGCTTGCGGCAACAC
CAAAAGCGGTGAAGTCTGCCTATGACAATGCTGAAAAACGTCTTCAGAAAGATCAGAACGG
TGCGGATATTCCGGGAAAGGATACTTTCACGAAAAATATCGGTGCCTGTCGTGCTTATAGCG 
GTGCTTTGAGCACTGACGCCGGAAACTGGACAACCGCTCAGTTTATTGACTGGCTAGAGTCT 
CAGGGAGCCTTTAATCATCCCTACTGGATGTGCAAGTGTTCCTGGTCATACGGTAATAACAA 
AATTATTACCGATACTGACTGTGGGACTATTCATCTTGCAGGTTGCGTGATTGAGGTTATGG 
GCGTTAAAGCTGCAATGACCATTCGTGTGACCACTCCGAGTACATCAAGCGGTGGTGGTACC 
ACCAGTGCGCAATTCACGTATATCAATCACGGAGCTGATTATGCGCCGGGCTGGCGACGCGA 
CTACAATACGAAAAATAAGCAACCGGCTTTTGCATTAGGGAAAACAGGAAATACGGTTGCA 
AATAATAAAGCGGTAGGATGGAACTGGGACAGTGGTGCTTATTGTGCACAGGATGGCGGAG 
CATCAAAAATGGTGCTGCATTTTTACACGGGTGAGGGAAGTTGTCCGGCAATGCAGTTTCTT 
GTGGATTATAAAAACAGGGGGATTTTTTACAGGTCGGCACGTGATGGGTATGGATTTGAGGC 
TGACTGGTCAGAGTTTTATACCACATCACGAAAGCCAACACCTGCGGATATTCTTGCTCTGG 
CATTATCAGGCGGAAGCATGTCAGGCAGCATAAAATTTATCAATGATGCCTTCCTGATTTGG 
GAAAGAAACACTGACTGGGCGAAAATTGGATTTAAAAATGATTCAGATGCTGATTCTGACTC 
ATACATGTGGTTTGAAACTGGTGATAATGGCAATGAATATTTTAAATGGCGCATCAGGTCTG 
GCAGCACAACAAAAGACCTGATGACGCTTAAGTCTGATGCACTACGGGTTACCGGGCAGGT 
GATACCATCAAATTTCAGCAATTTTGACTCCCGCTATGTCCGGGATATCCGGCTTGGTGGTGC 
CGCCACATACAAACCTGCGAACAATGGCATGACATGGACACATCAGGCACCGTCCGGGTGT 
GTATATACCGGCATTATTGTTCAGGATACCGGCTCAAACTCTGCCGATAACATTGGTGGCGT 
ATATTACAGACCGGTGCAGAAATACATTAACGGGACATGGTATAACGTGGCGCAGGTATAA 
STF90B accessory protein
(SEQ ID NO: 197)
ATGCAGCATTTAAAAAATATTACGGCGGGTAATCCAAAAACGGTTGAACAATATCAATTGA 
CAAAGGACTTTGATGTTGTCTGGTTTTTTTCAGAAGATGGTAAGAACTGGTACGAAGAACAA 
AAGTATTTTGCTGATGACACGATAAAAATAGCGTACGACAAAGATAATATCATCCGCTATGT 
GGAAAAGGATGTGACAGCTATCAGACCGGATGGATTAAGTGTTGTTGAAGTGGCGGATATT 
ACTGCTAACCGACGGGCGGATATTTCAGGGAACTGGATGTTTAAGGATGGCACAGTGATCA 
AACGAATTTATACGGCAGAGGAATTGCAACAGCAGGCAGAAAACAGGAAAGCCAGACTTCT 
TGCAGATGCTGAATCCGTGATTTTGCCGCTGGAGCGCGCTGTCAGGCTGAATATGGCAACAG 
AGGAGGAGCGTAGCAGACTGGAAAGATGGGAACGCTACAGCGTTCTGGTCAGTCGTGTGGA 
TCCTGCAAATCCCGAATGGCCGGAAATGCCGCAATAA 
STF117
(SEQ ID NO: 198)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGT
AATGGATGAGACTAATCGTAAATATACTGCGCAGGATGCCACCACAGCGCGAAAAGGGCTT
GTCCAGCTCAGTAGCGCCACCAACAGTGATTCTGAAACCCTCGCGGCAACGCCAAAAGCAG
TGAAGTCTGCCTATGACAATGCTGAAAAACGTCTTCAGAAAGATCAGAACGGTGCGGATATT
CCGGGAAAGGATACCTTCACGAAAAATATCGGTGCCTGTCGTGCTTATAGCGGCGCTTTGAG
CACTGAAGCCGGAAACTGGACAACCGCTCAGTTTATTGAATGGCTGGATTCCCGTGGTGCAT
TTAATCATCCGTACTGGATGTGCAAAGGCTCCTGGTCATATGCAAATAACAAAATCATTACG
GATACCGGATGTGGTGATATCCACCTGGCTGGTTGTGTCGTCGAGGTCATGGGAACTAAATC
TGCAATCACTATCCGAGTGACCACGCCGACAACATCAAGCGGTGGCGGTACAACCAGCGCG
CAATTCACTTACATTAATCATGGGGACGGCTACTCCCCCGGCTGGCGTCGTGACTGGAATCG
TCAGGGCGACGCAATGACCGGAACGATTAATCAGGATGGCGGAAGCCAGAATGCCTATATG
TCTACGGCCTTATGTTCAGGCACCAGAGGCGGCAAAAAATATCTCAGAAAGTTTCGTGGTGG
AGAAGGAGACACTATCTGGCATGAAACAGTACAGGGCGGGGTAGTTCGCTGGGCGACTGGT
AATACTGATGCTCAGGAAGAATTATCACTCAGCTCCGCTTATGGTCTCCGTTCAAGAGGTGA
GATTACATCAAGCAGTGCTAATGGTCTGCGCATTGCTTATGGCAATTATGGATTCTTTATCAG
GAATGATGGCAGCAGCACTTATTTTATGTTGACTAAATCAGGTGACAGATTAGGCACTTATA
ATAATTTAAGACCACTGATTATAAATGATGCCACGGGTGCTGTATCAATGGGGCATGGCCTG
AGTGTTACTGGTGATATTGCCTCAAGTACCAAAGTACGTGCCGGTAGCGGGAAAAAATTCAC
GGTCAGCAGCAGTAATACATCCACGAAGGAAGCCGCATTCAATTTGTGGGGAAACTCAAGT
CGTCCGGTGGTGGCTGAATTAGGTGATGATGCAGGCTGGCATTTTTACAGTCAGAGAAATAC
AGATAACAGCATCACTTTTGCTGTTAACGGGCAGGTATCACCATCTAACTATAGTAATTTTG
ATTCACGCTATGTCCGGGATATCCGGCTTGGTGGTGCTGCCACATACAAACCTGCGAACAAT
GGCATGACATGGACACATCAGGCACCGTCCGGGTGTGTATATTCCGGCATTATTGTTCAGGA
TACCGGCTCAAACTCTGCCGATAACATTGGTGGCGTATATTACAGACCGGTGCAGAAATACA
TTAACGGGACATGGTATAACGTGGCACAGGTATAA
STF117 accessory protein 1
(SEQ ID NO: 199)
ATGCAGCATTTGATAAATATAACCGCGGGTAATCCAAAAACGGTTGAACAATATCAATTGAC 
AAAGGACTTTGATGTTGTCTGGTTTTTTACAGAAGATGGTAAGAACTGGTACGAAGAACAAA 
AGTATTTTGCTGATGACACGATAAAAATAGCGTACGACAAGGATAATATTATCCGCTATGTG 
GAAAAAGATGTGACAGCTATCAGACCAGATGGATTAAGTGTGGTTGAAGTGGCGGATATTA 
CTGCTAACCGACGGGCGGACATTTCAGGGAACTGGATGTTTAAGGACGGCAAAGTGATTAA 
ACGCATTTATACGGCAGAGGAATTGCAGCAGCAGGCAGAAAACCGGAAAGCCAGACTTCTT 
GCAGATGCTGAATCCGTGATTTTGCCACTGGAGCGCGCTGTCAGGCTGAACATGGCAACAGA 
TGAGGAGCGTAGCCGACTGGAAGCATGGGAACGCTACAGTGTTCTGGTCAGCCGTGTGGAT 
CCTGCAAATCCTGAATGGCCGGAAATGCCGCAATAA 
O111
(SEQ ID NO: 200)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA 
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA 
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC 
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA 
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC 
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG 
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC 
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC 
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA 
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA 
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC 
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA 
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG 
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC 
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC 
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC 
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT 
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA 
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGT 
AATGGATGAGACTAATCGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACA 
GCACCAACCGCGCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGG 
CCGCGATTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCC 
GCAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTAAACA 
ACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAATAAATTACCG 
TATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTTGGCAGGGATATTCT 
GGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCCGGTGAGAATTCGGCATCAG 
GTGCATTACAGAAGAATCAAAACGGTGCAGACATTCCGGGCAAAGATACCTTTACCAAGAA 
TATCGGTGCTTGTCGTGCTTATTCGGCATGGCTTAATATCGGAGGTGATTCTCAGGTATGGAC 
TACGGCTCAGTTTATCTCTTGGCTCGAGAGTCAGGGTGCGTTTAATCATCCGTACTGGATGTG 
CAAAGGCTCTTGGGCGTACGCGAACAACAAAGTCATCACCGACACTGGTTGTGGTAACATCT 
GTCTGGCGGGTGCAGTAGTGGAAGTTATCGGTACGCGCGGTGCGATGACGATCCGTGTAACT 
ACTCCATCTACCTCCTCCGGTGGCGGTATCACCAACGCCCAGTTCACTTACATTAACCACGG 
CGATGCCTATGCTCCGGGCTGGCGCCGTGATTACAACACTAAAAACCAACAACCTGCGTTTG 
CACTGGGTCAGACGGGTAGTCGTGTGGCGAACGATAAAGCGGTCGGTTGGAATTGGAACTC 
TGGTGTGTACAACGCTGATATTAGTGGAGCTTCTACTCTGATCCTTCATTTTAACATGAATGC 
TGGAAGTTGTCCGGCAGTGCAGTTTCGTGTTAACTATCGTAATGGAGGAATCTTTTACCGCTC 
TGCACGTGACGGCTACGGCTTCGAAGCGAACTGGAGTGAATTTTACACGACCACTCGTAAGC 
CGAGTGCTGGAGATGTGGGAGCTTATACTCAGGCAGAATGCAATTCGCGTTTCATTACTGGT 
ATTCGTCTGGGAGGTTTAAGTTCCGTGCAGACTTGGAACGGTCCAGGTTGGAGTGATCGTAG 
TGGCTATGTTGTGACAGGCAGTGTTAACGGCAACCGTGACGAACTGATCGACACTACTCAAG 
CGCGTCCGATCCAGTACTGCATTAACGGAACTTGGTATAACGCGGGAAGTATCTAA 
O111 accessory protein
(SEQ ID NO: 201)
ATGATGCACTTAAAAAACATTACTGCTGGCAACCCTAAAACAAAAGAGCAATACCAGCTAA 
CGAAACAATTTAACATCAAATGGCTTTATTCAGAGGATGGAAAAAACTGGTATGAGGAACA 
AAAGAATTTCCAGCCAGACACTTTGAAAATGGTTTATGACCATAACGGCGTTATTATTTGTA 
TTGAAAAGGATGTTTCAGCAATTAATCCGGAAGGCGCAAGCGTCGTTGAATTACCTGATATT 
ACAGCAAATCGCCGTGCTGACATTTCGGGTAAATGGATGTTCAAAGATGGCGTAGTGGTAA 
AGCGTACTTACACAGAAGAAGAGCAACGTCAACAGGCGGAAAATGAAAAGCAAAGCCTGC 
TACAGCTCGTCAGGGATAAAACCCAGCTATGGGACAGTCAGCTACGGCTGGGCATCATTTCC 
GACGAGAATAAACAAAAATTAACAGAGTGGATGCTCTTTGCGCAGAAAGTCGAATCTACAG 
ACACTTCCAGCCTGCCAGTAACGTTTCCCGAACAACCAGAATGA 
DC1
(SEQ ID NO: 202)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGCAGC
ATATGACCTTGCTAACGGGAAATACACTGCACAGGACGCCACCACAGCGCGAAAAGGTCTT 
GTCCAGCTCAGTAGCGTCACCAACAGTGATTCTGAAACCCTCGCGGCAACGCCAAAAGCAG 
TGAAGTCTGCCTATGACAATGCTGAAAAACGTCTTCAGAAAGATCAGAACGGTGCGGATATT 
CCGGGAAAGGATACCTTCACGAAAAATATCGGTGCCTGTCGTGCTTATAGCGGCGCTTTGAG 
CACTGAAGCCGGAAACTGGACAACCGCGCAGTTTATTGACTGGCTAGAGTCTCAGGGAGCC 
TTTAATCATCCCTACTGGATGTGCAAGTGTTCCTGGTCATACGGTAATAACAAAATTATTACC 
GATACTGACTGTGGGACGATTCATCTTGCAGGTTGCGTGATTGAGGTTATGGGTGTTAAAGC 
AGCAATGACCATTCGTGTGACCACTCCGAGTACATCAAGCAGTGGTGGTACCACCAGTGCGC 
AATTCACGTATATCAATCACGGAGCTGATTATGCGCCGGGCTGGCGACGCGACTACAATACG 
AAAAATAAGCAACCGGCTTTTGCATTAGGGAAAACAGGAAATACGGTTGCAAATAATAAAG 
CAGTAGGATGGAACTGGGACAGTGGTGCTTATTGTGCACAGGATGGCGGAGCATCAAAAAT 
GGTGCTGCATTTTTACACGGGTGAGGGAAGTTGTCCGGCAATGCAGTTTCTTGTGGATTATA 
AAAACAGGGGGATTTTTTACAGGTCGGCACGTGATGGGTATGGATTTGAGGCTGACTGGTCA 
GAGTTTTATACCACATCACGAAAGCCAACACCTGCGGATATTCTTGCTCTGGCATTATCAGG 
CGGAAGCATGTCAGGCAGCATAAAATTTATCAATGATGCCTTCCTGATTTGGGAAAGAAACA 
CTGACTGGGCGAAAATTGGATTTAAAAATGATTCAGATGCTGATTCTGACTCATACATGTGG 
TTTGAAACTGGTGATAATGGCAATGAATATTTTAAATGGCGCATCAGGTCTGGCAGCACAAC 
AAAAGACCTGATGACGCTTAAGTCTGATGCACTACGGGTTACCGGGCAGGTGATACCATCA 
AATTTCAGCAATTTTGACTCCCGCTATGTCCGGGATATCCGGCTTGGTGGTGCCGCCACATAC 
AAACCTGCGAACAATGGCATGACATGGACACATCAGGCACCGTCCGGGTGTGTATATACCG 
GCATTATTGTTCAGGATACCGGCTCAAACTCTGCCGATAACATTGGTGGCGTATATTACAGA 
CCGGTTCAGAAATACATTAACGGGACGTGGTACAACGTGGCGCAGGTA 
DC1 accessory protein 1
(SEQ ID NO: 203)
ATGCAGCATTTGATAAATATAACGGCAGGTAATCCAAAAACGGTTGAACAATATCAATTGA 
CAAAGGACTTTGATGTTGTCTGGTTTTTTTCAGAAGATGGTAAGAACTGGTACGAAGAACAA 
AAGTATTTTGCTGATGACACGATAAAAATAGCGTACGACAAAGATAATATTATCCGCTATGT 
GGAAAAGGATGTGACAGCTATCAGACCAGATGGATTAAGTGTTGTTGAAGTGCCGGATATT 
ACTGCTAATCGACGGGCGGACATTTCAGGGGGCTGGATGTTTAAGGACGGCAAAGTGATTA 
AACGCATTTATACGGCAGAGGAATTGCAGCAGCAGGCAGAAAACCGGAAAGCCAGACTTCT 
TGCAGATGCTGAATCCGTGATTTTGCCGCTGGAGCGCGCGGTCAGACTGAACATGGCAACAG 
ATGAGGAGCGTAGCCGACTGGATGCATGGGAGCGTTACAGCGTTCTGGTCAGTCGTGTGGAT 
CCTGCAAATCCTGAATGGCCGGAAATGCCGCAATAA 
STF94A
(SEQ ID NO: 204)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG 
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC 
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC 
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC 
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT 
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA 
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGT 
AATGGATGAGACTAATCGTAAATATACCGCACAGGACGCCACCACAGCGCGAAAAGGCCTT 
GTTCAGCTGAGTAGCGCCATCAACAGCGATTCTGAAACGCTTGCGGCAACGCCAAAGGCGG 
TTAAGACAGCGTATGACCTTGCTAACAGGAAATACACTGCACAGGATGCCACCACAGCGCG 
AAAAGGTCTTGTCCAGCTAAGTAGCGCCACCAACAGTGATTCTGAAACGCTGGCCGCAACAT 
CAAAAGCGGTGAAGTCTGCCTATGACAATGCTGAAAAACGTCTTCAGAAAGATCAGAATGG 
TGCGGATATTCCGGGAAAGGATACCTTCACGAAAAATATCGGTGCCTGTCGTGCTTATAGCG 
GCGCTTTGAGCACTGAAGCCGGAAACTGGACAACCGCTCAGTTTATTGAATGGCTGGATTCC 
CGTGGTGCATTTAATCATCCGTACTGGATGTGCAAAGGCTCCTGGTCATATGCAAATAACAA 
AATCATTACGGATACCGGATGTGGTGATATCCACCTGGCTGGTTGTGTCGTCGAGGTCATGG 
GAACTAAATCTGCAATCACTATCCGAGTGACCACACCGACAACATCAAGCGGTGGCGGTAC 
AACCAGCGCACAATTCACTTACATTAATCATGGGGACGGCTACTCCCCCGGCTGGCGTCGTG 
ACTGGAATCGTCAGGGCGACGCAATGACCGGAACGATTAATCAGGACGGTGGAAGCCAGAA 
TGCCTATATGTCTACGGCCTTATGTTCAGGCACAAGAGGCGGCAAAAAATATCTCAGAAAGT 
TTCGTGGTGGAGAAGGAGACACTATCTGGCATGAAACAGTACAGGGCGGGGTAGTTCGTTG 
GGCGACTGGTAATACTGATGCTCAGGAAGAATTATCACTCAGCTCCGCTTATGGTCTCCGTT 
CAAGAGGTGAGATTACATCACTCAGTGCTAATGGTCTGCGCATTGCTTATGGCAATTATGGT 
TTCTTTATCAGGAATGATGGCAGCAGCACTTATTTTATGTTGACTAAATCAGGTGACAGATT 
AGGAACTTATAATAATTTAAGACCGCTGATTATAAATGATGCCACTGGTGCTGTATCAATGG 
GGCATGGCCTGAATGTTACTGGTGATATTGTCTCAAGTACCAAAGTACGTGCCGGTAGCGGG 
AAAAAATTCACGGTCAGCAGCAGTAATACATCCACGAAGGAAGCCGCATTCAATTTGTGGG 
GAAACTCAAGTCGTCCGGTGGTGGCTGAATTAGGTGATGATGCAGGCTGGCATTTTTACAGT 
CAGAGAAATACAGATAACAGCATCACTTTTGCTGTTAACGGGCAGGTATCACCATCTAACTA 
TGGCAACTTTGATTCACGCTATGTCCGGGATATCCGGCTTGGTGGTGCTGCCACATACAAAC 
CTGCGAACAATGGCATGACATGGACACATCAGGCACCGTCCGGGTGTGTATATTCCGGCATT 
ATTGTTCAGGATACCGGCTCAAACTCTGCCGATAACATTGGTGGCATATATTACAGACCGGT 
GCAGAAATACATTAACGGGACATGGTATAACGTAGCGCAGGTATAA 
>STF94A accessory protein
(SEQ ID NO: 205)
ATGCAGCATTTGATAAATATAATGGCGGGTAATCCAAAAACAGTTGAACAATATCAATTGAC 
AAAGGGCTTTGATGTTGTCTGGTTTTTTACAGAAGATGGTAAGAACTGGTACGAAGAACAAA 
AGTATTTTGCTGATGACACGATAAAAATAGCGTACGACAAAGATAATATCATCCGCTATGTG 
GAAAAGGATGTGACAGCTATCAGACCGGATGGATTAAGTGTGGTTGAAGTGGCGGATATTA 
CTGCTAACCGACGGGCGGATATTTCAGGGGGCTGGATGTTTAAGGACGGCAAAGTGATTAA 
ACGCATTTATACGGCGGAGGAATTACAGCAGCAGGCAGAAATTCGGAAAGCCAGACTTCTT 
GCAGATGCTGAATCCGTGATTTTGCCGCTGGAGCGCGCGGTCAGACTGAACATGGCAACAG 
AGGAGGAGCGCACACGGCTGGAGGCTTGGGAACGCTACAGCGTTCTGGTCAGTCGTGTGGA 
TCCTGCAAATCCTGAATGGCCGGAAATGCCGCAATAA 
STF69A
(SEQ ID NO: 206)
GCTTCTGCCACTGCATCAGCTAACAGTCAAAAAGCAGCAAAAACCAGTGAAACCAACGCAA
AGGCGAGCGAAACAGCGGCTGCGAACTCAGCGAAAGCATCGGCAGCAAGCCAGACGGCAG
CTAAAGCAAGCGAAGATGCAGCCAGAGAGTACGCAAGCCAGGCTGCGGAGCCGTATAAATA
TGTCTTACAGCCGTTACCTGAGGTGTGGATACCGTTTAACGATTCACTGGATATGATTACCG
GGTTTGCTCCTGGATATAAGAGCATCACAGTTGGTGACGATGTTATTGCATTGCCGTCTGAA
AAGGTTGTTTCATTTACCAGGGCGTCAACTGCAACGTATATAGATAAGTCTGGGTGTTTTGCT
GAATCAGCGATAAATGAACCACGTTTTGAAAAAGATGGTCTGCTCATTGAAGGTCAGAGAA
CGAATACTTTTTCTTATACGAATACACCAGTATCGTGGAACTATGACACTGCTAACTTAACTA
TTACCACGGGAGTTGATGAGTATGGTTTCAGTTATGGTTTGTTTGGCGTTAAAGAAACATCC
ACAACTGAAAGGGCGACATTAATTTCTACTGGATATACCAGGGTTATTTCAGTTTCGGCAAA
TGAATCAGTTACTTTATCCTGCAGAGTTAAAAAAGTAAGTGGGGATGGTATTATCACGTTGC
GTCCAAGAATATCATATGTTAACGACGATGGCTCAAGTAACACACTGACCGCTGGCGCATAT
ATTGATTGCGAGACTGGCGATATGTTGAGTTATTCTGGAGGTGAGGCGGCAACTTATAACAT
ATTCAGAGAGTCTAATGGATGGATTCGTGTTGAGTTTACCTACAAATCACCAGAAGCAAAAA
ATATGTATGGGCGTTTTGAGTTTGGAGCACATCAACGATCAATCAAGTCTGGCGATAAATTA
ATGTTAACAACCCCTCAATTCGAAAAGGGACTAAACGCGTCATCTTTTATCATCACAACAGA
GGTCGGTGCCACGAGAGCAAGTGACCAGGTAATCATACCTATACCTTTCAATTGGGCAACTC
CACCAGTTAGTGTTCTCATGGAAGTTAATGTTAATTGGGATTCTGAAATGCCTAATTTAGAA
GGCTCTGCGCGTTTGCTTAATATCTCAATTACAGGGGCGACGACTGAAGTTTCTGATGAAAG
TTATATGTATTTTGGTTTTACCACTCGTGGTAAAAGGCTAATTATCACCAATGGCAAAGGAA
CAAAAACAGAATATAAAGCATATGGGAATAGAGAGAAAAGGAAATTTGTTACTGGCTTTAA
GTTTACAGAAGATAAACAGTTGCAGGTTGTTGTTGATGGAATTTTAGGTGGCAGCTCCCCGT
CTCTGCATACATTGCAACGTTATACTGCCGGTAATATTAATATCGGTGGACAATCATCCAGT
GGCAACAGACACCTGTTCGGTCATGTGAAAAATTTACGCATTTGGCATAAAGAATTAACTGA
GGCACAAATGGGGGAGTCAATCTAA
>STF69A accessory protein 1
(SEQ ID NO: 207)
ATGAAAGATTTAACACTCAAATTTGAAGACAGGGCCGACTTTTCGGCCTTTATGGAGAGTAT 
TGGCTATTATGATGACGAGTCGATGCAGGATGATATTCTTATCGACGTGATAGGTAACGTGT 
ACAAAGAAACCGGAGAACTGACTGAAGATGGCGAACCGGTATGTGTTAAGGAAGACGGAT 
ATTTTGTAAACGTGCGCATCATTAATGATTCGCAAATATCGTCATTATTCGATGAATACGTGG 
TTGCTGTTGAGCATCAACTTCGTGGCTGGATGTGA 
>STF69A accessory protein 2
(SEQ ID NO: 208)
ATGGCTACATCGACAGTAATTCCTGATGACATCAAAACGCTAAAATCCGACGTTAGCAAATT 
AAAAAACGATCAAGGAAGCTACGCAACAAAATTATATGTAGACAGCAAAGATGAAATCGTT 
GGTGACTGGTCTGCTTCATGGTATCAGCAGGTATTGCCAACTAGCGGAGCTATATTTGGGAG 
AAAACTCCGCTCAACTCACAGGACGGCAGGTGTTGAGGATGCGTATTGCGAACTATACCTCA 
AAAAATGGATAGACAGTCCAGGTAACGCAATGGCGCGCCTTAACCTGAACGATAACGGGAC 
AAACATTTGCTGGGACTTTACCAACCTTTATGGCGGTACGATGATTTTTCCCGGTGACAGCG 
GATACCTCAAAATGGGTAACTGCCTTATGTCATACAGCAAGCGTGGAAGTAACGCGCTTATT 
AAATTTGATTACACCGACACATTACAGATCAAATATGCCAATCATGGGTCAACCATGACATT 
AAACACACAGGGAACCGCTTATGCTGGTGTTACTGCTCAATTGTGGGGCAACTCCAGCCGTC 
CTGTTGTTTATGAAGTCGGTGTTGATGGTGGCGCTTATATGTTCTATGCGCAGAAAAATACC 
GATAACACCTATATGTTAAGCGTTAATGGTGCATGTCATGCCACCGCATTTAACCAGCATTC 
CGACCGGGATCTGAAAGACAACATTCAGGTGATCGATAATGCAACCGACCGCATCCGTAAA 
ATGAACGGCTATACATACACGCTTAAAGAAAACGGTATGCCCTATGCTGGTGTCATTGCACA 
GGAAGCTCTGGAAGCAATCCCAGAAGTTGTAGGTTCCGCAATGAAATATCAGGACGGTGCG 
AGCGGATCGGAAGGTGAAGAAGGTGAACGTTATTACACAGTAGATTATTCTGGTGTTACTGG 
CTTGCTTGTTCAGGTAGCCAGAGAGTCAGACGACAGAATAACAGCACTGGAAGAAGAAAAC 
GCAGAATTAAGACAAAGATTATCTGCAATTGAGGCGGCGCTTGCGTCTAAATAA 
>STF118
(SEQ ID NO: 209)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGT
AATGGATGAGACTAATCGTAAAGCGCCATTAAACAGCCCTGCACTGACCGGAACGCCAACG
ACGCCAACTGCGCGACAGGGAACGAATAATACTCAGATCGCAAACACGGCTTTCGTTATGG
CCGCGATTGCCGCCCTTGTAGACTCGTCGCCTGACGCACTGAATACGCTGAACGAGCTGGCA 
GCGGCGCTGGGCAACGACCCGAATTTTGCTACCACTATGACTAATGCGCTTGCGGGTAAGCA 
ACCGAAAGATGCTACCCTGGCGGCGCTGGCGGGGCTTGCTACTGCGGCAGACAGGTTTCCGT 
ATTTTACGGGGAATGATGTTGCCAGTCTGGCAACTCTGACAAAAGTCGGGCGGGATATTCTT 
GCGAAATCGACCGTTTCCGCCGTTATCGAATATCTCGGTTTACAGGAAACGGTAAACCGAGC 
CGGGAACGCCGTGCAAAAAAATGGCGATACCTTGTCCGGTGGACTTACTTTTGAAAACGACT 
CAATCCTTGCCTGGATTCGAAATACTGACTGGGCGAAGATTGGATTTAAAAATGATGCCGAT 
GGTGACACTGATTCATATATGTGGTTTGAAACAGGTGACAACGGCAATGAATACTTCAAATG 
GAGAAGTCGCCAGAGCACCACAACAAAAGACCTGATGAATCTTAAATGGGATGCTCTGTAT 
GTTCTTGTTAAAGCCCTTTTCAGCAGTGAAGTAAAAATATCTACAGTCAATGCACTGAGGAT 
ATTTAATTCATCTTTTGGTGCTATTTTTCGCCGTTCTGAAGAAAACCTGTATATCATCCCTAC 
ACGAGAAAATGAGGGTGAAAATGGAGATATTGGGCCATTAAGGCCATTCGGCATCAACTTA 
AGAACAGGAGTTGTGTCTGTTGGTAATGGTGCCAGGATTGATGGCGGGCTGGCACTTGGCAC 
GAATAACGCGTTGGGTGGGAACTCTATTGTTCTTGGTGATAACGACACCGGATTTAAACAAA 
ATGGCGATGGTAATCTGGATGTTTATGCTAATAACGTCCATGTTATGCGCTTTGTTTCCGGAA 
GCATTCAAAGTAATAAGACCATAAATATTACGGGGCGTGTTAATCCCTCGGATTACGGTAAC 
TTTGATTCCCGCTATGTGAGAGATATCAGACTTGGCACACGTGTTGTCCAGACCATGCAGAA 
AGGGGTGATGTATGAGAAAGCAGGGCACGTAATTACCGGGCTTGGTATTGTCGGTGAAGTC 
GATGGTGATGACCCCGCAGTATTCAGGCCAATACAAAAATACATCAATGGCACATGGTATA 
ACGTCGCACAGGTGTAA 
>STF118 accessory protein
(SEQ ID NO: 210)
ATGCAGCATTTAAAAAATATTACTGCGGGTAATCCAAAAACTGTTGCCCAATATCAACTGAC 
AAAAAATTTTGATGTTATCTGGTTATGGTCCGAAGAGGGAAAAAACTGGTATGAGGAAGTA 
AGTAATTTTCAGGAAGACACGATAAAGATTGTTTACGACGAGAATAATATAATTGTCGGCAT 
CACCAGAGATGCTTCAACGCTTAACCCTGAAGGTTTCAGCGTTGTCGAGGTTCCTGATATTA 
CCTCCAACCGACGTGCTGATGACTCAGGTAAATGGATGTTTAAGGATGGTGCCGTGATTAAG 
CGGATTTATACGGCAGATGAACAGGAGCAACAGGCAGAATCACAAAAGGCAGCTTTACTTT 
CCGAAGCTGAATCCGTGATTTTGCCGCTGGAACGCGCTGTCAGGCTGAATATGGCGACGGAT 
GAGGAACGCAGCCGACTGGAAGCATGGGAACGCTACAGCGTTCTGGTCAGTCGTGTGGATC 
CTGCAAATCCCGAATGGCCGGAAATGCCGCAATAA 
K1F
(SEQ ID NO: 211)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA 
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA 
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC 
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA 
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC 
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG 
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC 
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC 
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA 
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA 
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC 
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA 
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG 
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC 
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGACGCAAAAACAGCGGCGGCGGGGAGTGC 
GTCAACGGCATCCACGAAGGCGACAGAGGCTGCGGGAAGTGCGGTATCAGCATCGCAGAGC 
AAAAGTGCGGCAGAAGCGGCGGCAATACGTGCAAAAAATTCGGCAAAACGTGCAGAAGAT 
ATAGCTTCAGCTGTCGCGCTTGAGGATGCGGACACAACGAGAAAGGGGATAGTGCAGCTCA 
GCAGTGCAACCAACAGCACGTCTGAAACGCTTGCTGCAACGCCAAAGGCGGTTAAGGTGGT 
AATGGATGAGACTAATCGTAAGGCACCTCTGGACAGTCCGGCACTGACCGGAACGCCAACA 
GCACCAACCGCGCTCAGGGGAACAAACAATACCCAGATTGCGAACACCGCTTTTGTACTGG 
CCGCGATTGCAGATGTTATCGACGCGTCACCTGACGCACTGAATACGCTGAATGAACTGGCC 
GCAGCGCTCGGGAATGATCCAGATTTTGCTACCACCATGACTAACGCGCTTGCGGGTAAACA 
ACCGAAGAATGCGACACTGACGGCGCTGGCAGGGCTTTCCACGGCGAAAAATAAATTACCG 
TATTTTGCGGAAAATGATGCCGCCAGCCTGACTGAACTGACTCAGGTTGGCAGGGATATTCT 
GGCAAAAAATTCCGTTGCAGATGTTCTTGAATACCTTGGGGCCGGTGAGAATTCGGGTGCGA 
AGGGCGATGGCGTTACCGACGACACTGCAGCGCTGACTTCCGCCCTGAACGATACTCCGGTG 
GGTCAGAAAATCAACGGTAACGGTAAAACTTATAAAGTTACGTCCCTGCCGGACATCTCCCG 
CTTTATCAACACCCGTTTCGTGTATGAACGTATCCCAGGCCAGCCGCTGTACTACGCATCGG
AAGAGTTCGTTCAGGGTGAGCTTTTTAAAATCACCGACACTCCGTATTATAACGCCTGGCCA
CAGGATAAGGCTTTCGTGTACGAAAACGTTATCTATGCTCCGTACATGGGTTCCGACCGTCA
CGGTGTCAGCCGACTGCACGTAAGCTGGGTGAAATCGGGCGACGATGGTCAGACCTGGAGC
ACGCCTGAGTGGCTGACCGACCTTCATCCGGACTATCCGACCGTTAACTATCACTGCATGAG
CATGGGCGTCTGTCGCAACCGTCTGTTCGCAATGATCGAAACCCGTACGCTGGCAAAAAACG
CTCTGACTAACTGCGCCCTGTGGGATCGTCCAATGAGCCGCTCTCTGCACCTGACGGGTGGT
ATTACCAAAGCAGCGAACCAGCGTTACGCCACCATTCACGTACCGGATCATGGTCTGTTCGT
TGGTGACTTTGTAAATTTCTCTAATTCTGCAGTTACCGGTGTGTCTGGCGACATGACCGTTGC
GACCGTAATCGATAAGGACAATTTCACCGTCCTGACCCCGAACCAGCAAACCTCTGATCTTA
ACAACGCTGGCAAGAACTGGCACATGGGCACTAGCTTTCACAAATCTCCGTGGCGTAAAAC
CGATCTGGGCCTGATCCCGTCTGTAACTGAAGTGCACTCCTTCGCGACCATTGATAACAACG
GTTTCGCTATGGGTTATCACCAAGGTGATGTTGCACCGCGTGAAGTCGGCCTCTTTTATTTTC
CGGACGCATTCAACAGCCCGTCCAACTACGTGCGCCGTCAGATTCCGTCTGAATATGAACCG
GACGCCTCCGAGCCGTGCATTAAGTACTATGACGGTGTGCTGTACCTGATTACCCGTGGCAC
CCGTGGTGATCGTCTGGGTTCATCTCTGCATCGCTCCCGCGACATTGGTCAGACGTGGGAAA
GTCTGCGCTTCCCGCACAATGTTCATCACACCACCCTGCCGTTCGCGAAAGTCGGCGATGAC
CTGATCATGTTTGGCTCCGAACGTGCTGAAAACGAATGGGAAGCGGGCGCCCCAGACGATC
GCTACAAGGCATCTTACCCGCGCACCTTCTACGCGCGTCTGAACGTGAACAACTGGAACGCA
GACGATATCGAATGGGTAAACATCACCGACCAGATCTACCAGGGTGGTATCGTGAACTCTG
GTGTGGGCGTTGGTTCCGTTGTAGTTAAAGATAACTACATCTATTATATGTTCGGCGGCGAA
GACCACTTCAACCCGTGGACTTACGGCGATAACTCCGCGAAAGACCCGTTCAAATCCGATGG
TCACCCTTCTGACCTCTATTGTTACAAAATGAAAATCGGTCCGGACAACCGTGTTTCCCGCG
ATTTTCGCTACGGCGCTGTTCCAAACCGTGCAGTTCCGGTATTCTTCGACACGAACGGCGTG
CGTACCGTTCCGGCTCCGATGGAATTCACCGGCGACCTGGGTCTGGGCCACGTAACCATTCG
TGCCTCCACCAGCTCTAACATCCGTTCCGAAGTACTCATGGAAGGTGAATACGGCTTTATCG
GTAAGTCTATCCCGACGGACAACCCGGCAGGTCAGCGTATCATCTTCTGCGGCGGTGAGGGT
ACCTCTAGCACCACCGGCGCGCAAATCACCCTGTACGGCGCTAACAACACCGACTCTCGTCG
TATCGTATACAACGGTGATGAACATCTGTTCCAGTCCGCAGACGTGAAACCGTACAACGACA
ACGTCACCGCACTGGGTGGTCCATCCAACCGTTTCACCACTGCGTACCTGGGTTCCAACCCG
ATCGTTACTAGCAATGGTGAACGCAAAACTGAACCGGTAGTGTTTGACGACGCTTTTCTGGA
CGCATGGGGCGATGTTCATTACATCATGTATCAGTGGCTGGATGCCGTGCAGCTGAAAGGTA
ACGACGCGCGTATCCACTTTGGTGTGATCGCACAGCAGATTCGCGATGTCTTCATCGCACAC
GGTCTGATGGATGAAAATAGTACTAACTGTCGCTATGCGGTGCTGTGCTATGACAAATACCC
GCGTATGACCGACACCGTGTTCTCGCACAATGAGATTGTTGAACATACCGATGAAGAAGGTA
ACGTGACTACTACCGAAGAACCGGTTTATACCGAAGTGGTTATTCACGAAGAAGGTGAAGA
ATGGGGCGTGCGTCCTGATGGTATCTTTTTCGCGGAGGCAGCGTACCAGCGTCGCAAACTGG
AACGCATCGAAGCTCGTCTGTCGGCACTGGAACAGAAA
STF66
(SEQ ID NO: 212)
ATGGCAGTAAAGATTTCAGGAGTCCTGAAAGACGGCACAGGAAAACCGGTACAGAACTGCA
CCATTCAGCTGAAAGCCAGACGTAACAGCACCACGGTGGTGGTGAACACGGTGGGCTCAGA
GAATCCGGATGAAGCCGGGCGTTACAGCATGGATGTGGAGTACGGTCAGTACAGTGTCATC
CTGCAGGTTGACGGTTTTCCACCATCGCACGCCGGGACCATCACCGTGTATGAAGATTCACA
ACCGGGGACGCTGAATGATTTTCTCTGTGCCATGACGGAGGATGATGCCCGGCCGGAGGTGC
TGCGTCGTCTTGAACTGATGGTGGAAGAGGTGGCGCGTAACGCGTCCGTGGTGGCACAGAG
TACGGCAGACGCGAAGAAATCAGCCGGCGATGCCAGTGCATCAGCTGCTCAGGTCGCGGCC
CTTGTGACTGATGCAACTGACTCAGCACGCGCCGCCAGCACGTCCGCCGGACAGGCTGCATC
GTCAGCTCAGGAAGCGTCCTCCGGCGCAGAAGCGGCATCAGCAAAGGCCACTGAAGCGGAA
AAAAGTGCCGCAGCCGCAGAGTCCTCAAAAAACGCGGCGGCCACCAGTGCCGGTGCGGCGA
AAACGTCAGAAACGAATGCTGCAGCGTCACAACAATCAGCCGCCACGTCTGCCTCCACCGC
GGCCACGAAAGCGTCAGAGGCCGCCACTTCAGCACGAGATGCGGTGGCCTCAAAAGAGGCA
GCAAAATCATCAGAAACGAACGCATCATCAAGTGCCGGTCGTGCAGCTTCCTCGGCAACGG
CGGCAGAAAATTCTGCCAGGGCGGCAAAAACGTCCGAGACGAATGCCAGGTCATCTGAAAC
AGCAGCGGAACGGAGCGCCTCTGCCGCGGCAGCTTCTGCCACTGCAGCAGCCAACAGTCAA
AAAGCTGCAAAAACCAGTGAAACCAACTCAAAGGCGAGCGAAACAGCGGCTGCGAACTCA
GCGAAAGCATCGGCAGCAAGCCAGACGGCTGCAAAAGCAAGTGAGGATGCAGCCAGAGAG
TATGCAAGCCAGGCTGCGGAGCCGTATAAACAAGTTTTGCAGCCGCTTCCCGATGTGTGGAT
ACCGTTTAACGATTCACTGGATATGATTACGGGCTTTTCGCCGTCATATAAAAAGATTGTTAT
TGGTGATGATGAAATAACGATGCCTGGCGATAAGGTTGTAAAGTTTAAACGCGCATCGAAA
GCAACCTATATTAATAAATCTGGTGTGCTGACAGAGGCTGCCATTGACGAGCCACGATTTGA
ACGTGATGGCCTGCTTATTGAGGGGCAAAGAACAAACTACATGCTCAATTCGGAAAACCCT
GCCAGTTGGGGGCGATCGTCAAATATGGATGTTCCCGAAACCGGGACGGATAGTTTTGGTTT
TACCTATGGAAAGTTTGTCTGCAACGATTCTCTGATTGGGCAAACCTCAGCCATTAATATGG
CATCAATTGCTGCAACAAAGTCAGTTGATGTCTCAGGCGATAATAAATACGTGACAACCTCA
TGTCGTTTTAAAACAGAACTGCAGGTAAGGTTGCGTATCCGATTTGATAAATATGACGGTAG
CGCAACAACTTTTCTTGGTGATGCGTATATTGATACACAAACGCTTGAAATTAATATGACAG
GTGGTGCTTCCGGTAGAATTACGGCACGAGTCAGGAAGGATGAAACTACAGGATGGATTTTT
GCTGAGGCAACAATTCAGGCAATTGATGGTGAGTTAAAAATAGGCTCTCAGATACAGTATTC
ACCTAAGCAGGGAGGGGCAACCGTATCAGGTGACTATATTTATCTGGCTACCCCACAAGTAG
AGAATGGGGCTTGTGTATCATCTTTTATTATATCAGGAACGACGGCGGCGACTCGTGCGAGT
GATATGGTTACGATCCCGACCGAAAACAACATTTATAACAGACCGCTTACTTGTTTGGTCGA
GGTTAACAGGAATTGGGGCGATATTCCTCCTAATGTAGCACCGCGTATTTTTGATTTTTCTGG
TGTGCCGCCTATTGAGTCAATCACATACGCTTTTAACACAACCGAGAAATATTACGGTCAGC
TTTATATGCAAACTTATAAAGCGTCGACAAGTAGTTACGTTTCTAGTTTGTTTACTGGTCGAA
CGGATGTTCGAAAACTCATTGGTGGTTTTAATATTTATTCTGATGGTACTAAACGAGTAGTTT
CTAACGGTGAGGCTACTAAAACCATGAAAACGGAATGGACGGGCGTAAAAACGCGGACCTT
TATTCGAATAGGAGGTCAAGCCACATCAGGGACACGTCATCTATTCGGCCATTTGAGAAATC
TTCGTCTCTGGCATAAAGAATTAACTGATGCGCAAATGGGGGAGAGTATTAAATGA
STF66 accessory protein
(SEQ ID NO: 213)
ATGAAAGATTTAACACTCAAATTTGCCGACAGGGCCGACTTTTCGGCCTTTATGGAGAGTAT 
TGGCTATTATGATGACGAGTCGATGCAGGATGATATTCTTATTGACGTGATAGGTAACGTGT 
ACAAAGAAACCGGAGAACTGACTGAAGATGGCGAACCGGTATGTGTTAAGGAAGACGGAT 
ATTTTGTAAACGTGCGCATCATTAATGATTCGCAAATATCGTCATTATTCGATGAATACGTGG 
TTGCTGTTGAGCATCAACTTCGTGGCTGGATGTGA 
gpJ VARIANT
1A2
(SEQ ID NO: 214)
MGKGSSKGHTPREAKDNLKSTQLLSVIDAISEGPIEGPVDGLKSVLLNSTPVLDTEGNTNISGVTV
VFRAGEQEQTPPEGFESSGSETVLGTEVKYDTPITRTITSANIDRLRFTFGVQALVETTSKGDRNPS
EVRLLVQIQRNGGWVTEKDITIKGKTTSQYLASVVMGNLPPRPFNIRMRRMTPDSTTDQLQNKT
LWSSYTEIIDVKQCYPNTALVGVQVDSEQFGSQQVSRNYHLRGRILQVPSNYNPQTRQYSGIWD
GTFKPAYSNNMAWCLWDMLTHPRYGMGKRLGAADVDKWALYVIGQYCDQSVPDGFGGTEPR
ITCNAYLTTQRKAWDVLSDFCSAMRCMPVWNGQTLTFVQDRPSDKTWTYNRSNVVMPDDGAP
FRYSFSALKDRHNAVEVNWIDPNNGWETATELVEDTQAIARYGRNVTKMDAFGCTSRGQAHR
AGLWLIKTELLETQTVDFSVGAEGLRHVPGDVIEICDDDYAGISTGGRVLAVNSQTRTLTLDREIT
LPSSGTALISLVDGSGNPVSVEVQSVTDGVKVKVSRVPDGVAEYSVWELKLPTLRQRLFRCVSIR
ENDDGTYAITAVQHVPEKEAIVDNGAHFDGEQSGTVNGVTPPAVQHLTAEVTADSGEYQVLAR
WDTPKVVKGVSFLLRLTVTADDGSERLVSTARTTETTYRFTQLALGNYRLTVRAVNAWGQQGD
PASVSFRIAAPAAPSRIELTPGYFQITATPHLAVYDPTVQFEFWFSEKQIADIRQVETSTRYLGTAL
YWIAASINIKPGHDYYFYIRSVNTVGKSAFVEAVGRASDDAEGYLDFFKGKITESHLGKELLEKV
ELTEDNASRLEEFSKEWKDASDKWNAMWAVKIEQTKDGKHYVAGIGLSMEDTEEGKLSQFLV
AANRIAFIDPANGNETPMFVAQGNQIFMNDVFLKRLTAPTITSGGNPPAFSLTPDGKLTAKNADIS
GNVNANSGTLNNVTINENCRVLGKLSANQIEGDLVKTVGKAFPRDSRAPERWPSGTITVRVYDD
QPFDRQIVIPAVAFSGAKHEKEHTDIYSSCRLIVRKNGAEIYNRTALDNTLIYSGVIDMPAGHGHM
TLEFSVSAWLVNNWYPTASISDLLVVVMKKATAGITIS
STFs
WT STF accessory protein 1
(SEQ ID NO: 215)
MAFRMSEQPRTIKIYNLLAGTNEFIGEGDAYIPPHTGLPANSTDIAPPDIPAGFVAVFNS 
DEASWHLVEDHRGKTVYDVASGDALFISELGPLPENFTWLSPGGEYQKWNGTAWVKDTEA 
EKLFRIREAEETKKSLMQVASEHIAPLQDAADLEIATKEETSLLEAWKKYRVLLNRVDTS 
TAPDIEWPAVPVME 
SIED6
(SEQ ID NO: 216)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIADPASVPPLPDIW
LPLNDSLEAITGYAPGYKTITIGSDEITVPVNGICQFSRASSATYIDKSGHITVAGNNVP
RFEKYGLLIENQRTNMFVNSFNPDAWNKSGGISVTSSTDEFEFKYGRFTVGSDIAGTTTG
RNICTVAGNRGIDVTGDDQYSKGPYVTASFRVRSDLNVRARIRFERYNSEGYTFLCDAYL
SLQTHELQITGDNAQLLTANFEIDPGSGWIYFQATLKCLPEWGMVGTQLQIAADRAVGSF
ATGDWIEVTTPQFEYGACATSFIITTTEPATRASDLCKFPLMKNMYTMPFTFMVEVHKNW
FIAHNAAPRVIDTENHQSGAPFIMGFGSSGTISQDGYPYCDIGGANRRVYESCGVRDLVM
GFRVKADGMTCSFANKHISTETKTVWKYIREAAVIRIGGQTTTGLRHLNGHIKNLRFWNR
ALSDTQLKEYV
SIED6 accessory protein 1
(SEQ ID NO: 217)
MRDITLRFDNREQFNAIVYDSGLFSLEEENGILVDVIGRVIDYEEPENERCTGIDRGGFF 
VNMRIVDSSKNISSLMPFITTDQHVRTWA 
SIED6 accessory protein 2
(SEQ ID NO: 218)
MVTKTVIPDDIKTLKSDVSKLKNDQGSYATKSYVDSKDETVGDWSASWYQQVLPTSGAIF 
GRKLRSTHRTAGVEDAYCELYLKKWIDSPGNAMARLNLNDNGENICWDFTNLYGGTMIFP 
GTSGYLKMGNCLMSYGVRGSNALIKFDNTDSLQIKYANHGSTMTLNTQGTAYSGVSTLLW 
GNSSRPVVYEIRDDGGLFLFYAQRNPDKTYQLEINGPCKATSFDQVSDRDLKENIRVIDN 
ATERIRLMNGYTYRLKSNGMPYAGVIAQEALNAIPESVGSTIKYKSGDNGSDGE 
SIEA11
(SEQ ID NO: 219)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKAANDNANSRLAKNQNGADIQDKSAFLDNVGVTSLT
FMKNNGEMPVDADLNTFGSVKAYSGIWSKATSTNATLEKNFPEDNAVGVLEVFTGGNFAG
TQRYTTRDGNLYIRKLIGTWNGNDGPWGAWRHVQAVTRALSTTIDLNSLGGAEHLGLWRN
SSSAIASFERHYPEQGGDAQGILEIFEGGLYGRTQRYTTRNGTMYIRGLTAKWDAENPQW
EDWNQIGYQTSSTFYEDDLDDLMSPGIYSVTGKATHTPIQGQSGFLEVIRRKDGVYVLQR
YTTTGTSAATKDRLYERVFLGGSFNAWGEWRQIYNSNSLPLELGIGGAVAKLTSLDWQTY
DFVPGSLITVRLDNMTNIPDGMDWGVIDGNLINISVGPSDDSGSGRSMHVWRSTVSKANY
RFFMVRISGNPGSRTITTRRVPIIDEAQTWGAKQTFSAGLSGELSGNAATATKLKTARKI
NNVSFDGTSDINLTPKNIGAFASGKTGDTVANDKAVGWNWSSGAYNATIGGASTLILHFN
IGEGSCPAAQFRVNYKNGGIFYRSARDGYGFEADWSEFYTTTRKPTAGDVGALPLSGGQL
NGALGIGTSSALGGNSIVLGDNDTGFKQNGDGNLDVYANSVHVMRFVSGSVQSNKTINIT
GRVNPSDYGNFDSRYVRDVRLGTRVVQTMQKGVMYEKAGHVITGLGIVGEVDGDDPAVFR
PIQKYINGTWYNVAQV
SIEA11 accessory protein 1
(SEQ ID NO: 220)
MQHLKNITAGNPKTVAQYQLTKNFDVIWLWSEEGKNWYEEVSNFQEDTIKIVYDENNIIV 
GITRDASTLNPEGFSVVEVPDITANRRADDSGKWMFKDGAVIKRIYTADEQLQLAELQKS 
ALLSEAETIIQPLERSVRLNMATDEERSRLEAWERYSVLVSRVDPANPEWPEMPQ 
EB6
(SEQ ID NO: 221)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKIAMDNANARLAKDRNGADIPNKPLFIQNLGLQETV
NKAGNAVQKTGDTLSGGLTFENDSILAWIRNTDWAKIGFKNDADSDTDSYMWFETGDNGN
EYFKWRSRQSTTTKDLMNLKWDALYVLVNAIVNGEVISKSANGLRIAYGNYGFFIRNDGS
NTYFMLTNSGDNMGTYNGLRPLWINNATGAVSMGRGLNVSGETLSDRFAINSSNGMWIQM
RDNNAIFGKNIVNTDSAQALLRQNHADRKFMIGGLGNKQFGIYMINNSRTANGTDGQAYM
DNNGNWLCGAQVIPGNYGNFDSRYVRDVRLGTRVVQLMARGGRYEKAGHAITGLRIIGEV
DGDDEAIFRPIQKYINGTWYNVAQV*
EB6 accessory protein 1
(SEQ ID NO: 222)
MQHLKNIKSGNPKTKEQYQLTKNFDVIWLWSEDGKNWYEEVNNFQDDTIKIVYDENNIIV
AITKDASTLNPEGFSVVEIPDITANRRADDSGKWMFKDGAVVKRIYTADEQQQQAESQKA
ALLSEAENVIQPLERAVRLNMATDEERARLESWERYSVLVSRVDTAKPEWPQKPE*
AH11L
(SEQ ID NO: 223)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKAANDNANSRLAKNQNGADIQDKSVFLDNVGVTSLT
FMKNNGEMPLDADLNTFGPVKAYLGIWSKATSTNATLEKNFPEDNAVGVLEVFAAGNFAG
TQRFTTRDGNVYMRKLANKWNGTDGPWGVWRHTQSATRPLSTTIDLNTLGAAEHLGLWRN
SSSAIASYERNYPEEGGFAQGTLEILEGGNYGRTQRYTTRRGNMYVRCLAASWDASNPQW
EPWLRVGHQSESRYYEGDLNDVTSPGIYSVTGKATNGPVLDGNGVTVLGILEVLRRFDGV
NVWQRYTTAGTGTTLKGRTFERVFTGSSWSEWREVYTSYSLPLNLGIGGAVAKLTSLDWQ
TYDFVPGSLITVRLDNMTNIPDGMDWGVIDGNLINIAVGPSDDSGTGRSMHVWRSTVSKA
NYRFFMVRISGNPGSRTITARRVPIIDEAQTWGAKQTFSAGLSGELSGNAATATKLKTAR
KINNVSFDGTSDINLTPKNIGAFASGKTGDTVANDKAVGWNWSSGAYNATTGGASTLILH
FNIGEGSCPAAQFRVNYKNGGIFYRSARDGYGFEADWSEFYTTTRKPTAGDVGALPLSGG
QLNGALGIGTSSALGGNSIVLGDNDTGFKQNGDGNLDVYANSVHIMRFVSGSIQSNKTIN
ITGRVNPSDYGNFDSRYVRDIRLGGAATYKPANNGMTWTHQAPSGCVYSGIIVQDTGSNS
ADNIGGVYYRPVQKYINGTWYNVAQV
AH11L accessory protein 1
(SEQ ID NO: 224)
MQHLKNITAGNPKTVEQYQLTKGFDVVWFFSEDGKNWYEEQKYFADDTIKIAYDKDNIIR
YVEKDVTAIRPDGLSVVEVADITANRRADISGGWMFKDGKVIKRIYTAEELLQQAENRKA
RLLADAESVILPLERAVRLNMATDEERSRLDAWERYSVLVSRVDPANPEWPEMPQ
WW55 3.0 accessory protein 1
(SEQ ID NO: 225)
MAISSGWVGSSAVSETGQRWMSAAMQAVRLGRPAYMSAMVGRSKEIHYSIGASNSYNKDT
LINWMKAQGSTPVVITITGNIVSQSTGVPCLDFPSSLTNEYVTLIINSGVHVLGRGGNGG
SNSAGGAGGNAINNGIGTRLRINNNGIIGGGGGGGAGARYNPFPQMDMKFGGGGGRPFGA
AGAAGGGAAAASAGTISAPGKGTVSGVHYGGDGGDLGAAGKSSYIKGGTGGTVHSGGAAG
KAVTGNAPRWDKVGTIYGARV
WW55 3.0 accessory protein 2
(SEQ ID NO: 226)
MSNQHEQMINVLKVRLFDTQEKAAFLEGQLKDRERVLMELVRILGIQPDENGTVSLDAIV
EEVKALLPKDEAAEDAEEEVELITEA
STF68B
(SEQ ID NO: 227)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAAASAT
ASANSQKAAKTSETNAKTSETAAANSAKASAASQTAAKASEDAAREYASQAAEPYKQVLQ
PLPDVWIPFNDSLEMITGFAPGYKKVTIGDDVITFPSEKVVSFTRSTSATYINKSGSFAF
AEINEPRFEKEGLLIEGQRTNTFTNSNNPSLWNYDDKNIEITTSVDEYGFKYGLFDVKET
STTERATIISTGYSRVIDVAANESVTLSCRVKKINGEGIITLRPRISFVNDDGTSNTLVA
GSYIDCETGDVLGFSGGDAVNHVIYREANGWLRVEFTYKSPEAKSMYGRFEMGADKRAIK
KGDQIMFTTPQFEKGSCASSFIVTSDVAVTRASDVVIMPIRLNWSTPPLSVLMEVNINWD
KMPNSEGSARLLNVSITGATTDVADESYMYFGFTSGGARSIITNGKGTKTEYKAYCNRTT
RRFIAGFKFTEQKELRAVINGNFGAVDVSQHTRQRYTEGPINIGGQSISGNRHLFGHVRN
LRIWHKELTDAQMGERI
STF68B accessory protein 1
(SEQ ID NO: 228)
MRDLTLKFINKADFSAFMDSIGYEDDEVMQNNVLIDVIGNVYKETGELTEDGEPVCVKED 
GYFVNVRIINDAKKSSIFDKYAVVVEHQLRGWM 
STF68B accessory protein 2
(SEQ ID NO: 229)
MATSTVIPDDIKTLKSDVSKLKNDQGSYATKSYVDSKDETVGDWSASWYQQVLPTSGAIF 
GRKLRSTHRTAGVEDAYCELYLKKWIDSPGNAMARLNLNDNGTNICWDFTNLYGGTMIFP 
GDSGYLKMGNCLMSYSKRGSNALIKFDYTDTLQIKYANHGSTMTLNTQGTAHAGVTTRLW 
GNSSRPVVYEVGVDEALYMFYAQKTTSNTYELTVNGACNASAFNQGSDRDLKDNIQVIDN 
ATDRIRKMNGYTYTLKENGMPYAGVIAQETLEAIPEAVGAMMKYPDGGSGLDGEEGERYY 
TVDYSGVTGLLVQVARESDDRITALEEENAELRQRLSAIEAALASK 
STF90B
(SEQ ID NO: 230)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKVVMDETNRKYTAQDATTARKGLVQLSSVTNSDSET
LAATPKAVKTAYDLANGKYTAQDATTARKGLVQLSSATNSDSETLAATPKAVKSAYDNAE
KRLQKDQNGADIPGKDTFTKNIGACRAYSGALSTDAGNWTTAQFIDWLESQGAFNHPYWM
CKCSWSYGNNKIITDTDCGTIHLAGCVIEVMGVKAAMTIRVTTPSTSSGGGTTSAQFTYI
NHGADYAPGWRRDYNTKNKQPAFALGKTGNTVANNKAVGWNWDSGAYCAQDGGASKMVL
HFYTGEGSCPAMQFLVDYKNRGIFYRSARDGYGFEADWSEFYTTSRKPTPADILALALSGG
SMSGSIKFINDAFLIWERNTDWAKIGFKNDSDADSDSYMWFETGDNGNEYFKWRIRSGST
TKDLMTLKSDALRVTGQVIPSNFSNFDSRYVRDIRLGGAATYKPANNGMTWTHQAPSGCV
YTGIIVQDTGSNSADNIGGVYYRPVQKYINGTWYNVAQV
STF90B accessory protein
(SEQ ID NO: 231)
MQHLKNITAGNPKTVEQYQLTKDFDVVWFFSEDGKNWYEEQKYFADDTIKIAYDKDNIIR
YVEKDVTAIRPDGLSVVEVADITANRRADISGNWMFKDGTVIKRIYTAEELQQQAENRKA
RLLADAESVILPLERAVRLNMATEEERSRLERWERYSVLVSRVDPANPEWPEMPQ
STF117
(SEQ ID NO: 232)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKVVMDETNRKYTAQDATTARKGLVQLSSATNSDSET
LAATPKAVKSAYDNAEKRLQKDQNGADIPGKDTFTKNIGACRAYSGALSTEAGNWTTAQF
IEWLDSRGAFNHPYWMCKGSWSYANNKIITDTGCGDIHLAGCVVEVMGTKSAITIRVTTP
TTSSGGGTTSAQFTYINHGDGYSPGWRRDWNRQGDAMTGTINQDGGSQNAYMSTALCSGT
RGGKKYLRKFRGGEGDTIWHETVQGGVVRWATGNTDAQEELSLSSAYGLRSRGEITSSSA
NGLRIAYGNYGFFIRNDGSSTYFMLTKSGDRLGTYNNLRPLIINDATGAVSMGHGLSVTG
DIASSTKVRAGSGKKFTVSSSNTSTKEAAFNLWGNSSRPVVAELGDDAGWHFYSQRNTDN
SITFAVNGQVSPSNYSNFDSRYVRDIRLGGAATYKPANNGMTWTHQAPSGCVYSGIIVQD
TGSNSADNIGGVYYRPVQKYINGTWYNVAQV
STF117 accessory protein 1
(SEQ ID NO: 233)
MQHLINITAGNPKTVEQYQLTKDFDVVWFFTEDGKNWYEEQKYFADDTIKIAYDKDNIIR 
YVEKDVTAIRPDGLSVVEVADITANRRADISGNWMFKDGKVIKRIYTAEELQQQAENRKA 
RLLADAESVILPLERAVRLNMATDEERSRLEAWERYSVLVSRVDPANPEWPEMPQ 
O111
(SEQ ID NO: 234)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTAPTALRGTNNTQI
ANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAGKQPKNATLTALAG
LSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAGENSASGALQKNQNGA
DIPGKDTFTKNIGACRAYSAWLNIGGDSQVWTTAQFISWLESQGAFNHPYWMCKGSWAYA
NNKVITDTGCGNICLAGAVVEVIGTRGAMTIRVTTPSTSSGGGITNAQFTYINHGDAYAP
GWRRDYNTKNQQPAFALGQTGSRVANDKAVGWNWNSGVYNADISGASTLILHFNMNAGSC
PAVQFRVNYRNGGIFYRSARDGYGFEANWSEFYTTTRKPSAGDVGAYTQAECNSRFITGI
RLGGLSSVQTWNGPGWSDRSGYVVTGSVNGNRDELIDTTQARPIQYCINGTWYNAGSI
O111 accessory protein
(SEQ ID NO: 235)
MMHLKNITAGNPKTKEQYQLTKQFNIKWLYSEDGKNWYEEQKNFQPDTLKMVYDHNGVII
CIEKDVSAINPEGASVVELPDITANRRADISGKWMFKDGVVVKRTYTEEEQRQQAENEKQ
SLLQLVRDKTQLWDSQLRLGIISDENKQKLTEWMLFAQKVESTDTSSLPVTFPEQPE
DC1
(SEQ ID NO: 236)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKAAYDLANGKYTAQDATTARKGLVQLSSVTNSDSET
LAATPKAVKSAYDNAEKRLQKDQNGADIPGKDTFTKNIGACRAYSGALSTEAGNWTTAQF
IDWLESQGAFNHPYWMCKCSWSYGNNKIITDTDCGTIHLAGCVIEVMGVKAAMTIRVTTP
STSSSGGTTSAQFTYINHGADYAPGWRRDYNTKNKQPAFALGKTGNTVANNKAVGWNWDS
GAYCAQDGGASKMVLHFYTGEGSCPAMQFLVDYKNRGIFYRSARDGYGFEADWSEFYTTS
RKPTPADILALALSGGSMSGSIKFINDAFLIWERNTDWAKIGFKNDSDADSDSYMWFETG
DNGNEYFKWRIRSGSTTKDLMTLKSDALRVTGQVIPSNFSNFDSRYVRDIRLGGAATYKP
ANNGMTWTHQAPSGCVYTGIIVQDTGSNSADNIGGVYYRPVQKYINGTWYNVAQV
DC1 accessory protein 1
(SEQ ID NO: 237)
MQHLINITAGNPKTVEQYQLTKDFDVVWFFSEDGKNWYEEQKYFADDTIKIAYDKDNIIR 
YVEKDVTAIRPDGLSVVEVPDITANRRADISGGWMFKDGKVIKRIYTAEELQQQAENRKA 
RLLADAESVILPLERAVRLNMATDEERSRLDAWERYSVLVSRVDPANPEWPEMPQ 
STF94A
(SEQ ID NO: 238)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKVVMDETNRKYTAQDATTARKGLVQLSSAINSDSET
LAATPKAVKTAYDLANRKYTAQDATTARKGLVQLSSATNSDSETLAATSKAVKSAYDNAE
KRLQKDQNGADIPGKDTFTKNIGACRAYSGALSTEAGNWTTAQFIEWLDSRGAFNHPYWM
CKGSWSYANNKIITDTGCGDIHLAGCVVEVMGTKSAITIRVTTPTTSSGGGTTSAQFTYI
NHGDGYSPGWRRDWNRQGDAMTGTINQDGGSQNAYMSTALCSGTRGGKKYLRKFRGGEGD
TIWHETVQGGVVRWATGNTDAQEELSLSSAYGLRSRGEITSLSANGLRIAYGNYGFFIRN
DGSSTYFMLTKSGDRLGTYNNLRPLIINDATGAVSMGHGLNVTGDIVSSTKVRAGSGKKF
TVSSSNTSTKEAAFNLWGNSSRPVVAELGDDAGWHFYSQRNTDNSITFAVNGQVSPSNYG
NFDSRYVRDIRLGGAATYKPANNGMTWTHQAPSGCVYSGIIVQDTGSNSADNIGGIYYRP
VQKYINGTWYNVAQV 
STF94A accessory protein
(SEQ ID NO: 239)
MQHLINIMAGNPKTVEQYQLTKGFDVVWFFTEDGKNWYEEQKYFADDTIKIAYDKDNIIR
YVEKDVTAIRPDGLSVVEVADITANRRADISGGWMFKDGKVIKRIYTAEELQQQAEIRKA
RLLADAESVILPLERAVRLNMATEEERTRLEAWERYSVLVSRVDPANPEWPEMPQ
STF69A
(SEQ ID NO: 240)
ASATASANSQKAAKTSETNAKASETAAANSAKASAASQTAAKASEDAAREYASQAAEPYK
YVLQPLPEVWIPFNDSLDMITGFAPGYKSITVGDDVIALPSEKVVSFTRASTATYIDKSG
CFAESAINEPRFEKDGLLIEGQRTNTFSYTNTPVSWNYDTANLTITTGVDEYGFSYGLFG
VKETSTTERATLISTGYTRVISVSANESVTLSCRVKKVSGDGIITLRPRISYVNDDGSSN
TLTAGAYIDCETGDMLSYSGGEAATYNIFRESNGWIRVEFTYKSPEAKNMYGRFEFGAHQ
RSIKSGDKLMLTTPQFEKGLNASSFIITTEVGATRASDQVIIPIPFNWATPPVSVLMEVN
VNWDSEMPNLEGSARLLNISITGATTEVSDESYMYFGFTTRGKRLIITNGKGTKTEYKAY
GNREKRKFVTGFKFTEDKQLQVVVDGILGGSSPSLHTLQRYTAGNINIGGQSSSGNRHLF
GHVKNLRIWHKELTEAQMGESI
STF69A accessory protein 1
(SEQ ID NO: 241)
MKDLTLKFEDRADFSAFMESIGYYDDESMQDDILIDVIGNVYKETGELTEDGEPVCVKED
GYFVNVRIINDSQISSLFDEYVVAVEHQLRGWM
STF69A accessory protein 2
(SEQ ID NO: 242)
MATSTVIPDDIKTLKSDVSKLKNDQGSYATKLYVDSKDEIVGDWSASWYQQVLPTSGAIF
GRKLRSTHRTAGVEDAYCELYLKKWIDSPGNAMARLNLNDNGTNICWDFTNLYGGTMIFP
GDSGYLKMGNCLMSYSKRGSNALIKFDYTDTLQIKYANHGSTMTLNTQGTAYAGVTAQLW
GNSSRPVVYEVGVDGGAYMFYAQKNTDNTYMLSVNGACHATAFNQHSDRDLKDNIQVIDN
ATDRIRKMNGYTYTLKENGMPYAGVIAQEALEAIPEVVGSAMKYQDGASGSEGEEGERYY
TVDYSGVTGLLVQVARESDDRITALEEENAELRQRLSAIEAALASK
STF118
(SEQ ID NO: 243)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLNSPALTGTPTTPTARQGTNNTQI
ANTAFVMAAIAALVDSSPDALNTLNELAAALGNDPNFATTMTNALAGKQPKDATLAALAG
LATAADRFPYFTGNDVASLATLTKVGRDILAKSTVSAVIEYLGLQETVNRAGNAVQKNGD
TLSGGLTFENDSILAWIRNTDWAKIGFKNDADGDTDSYMWFETGDNGNEYFKWRSRQSTT
TKDLMNLKWDALYVLVKALFSSEVKISTVNALRIFNSSFGAIFRRSEENLYIIPTRENEG
ENGDIGPLRPFGINLRTGVVSVGNGARIDGGLALGTNNALGGNSIVLGDNDTGFKQNGDG
NLDVYANNVHVMRFVSGSIQSNKTINITGRVNPSDYGNFDSRYVRDIRLGTRVVQTMQKG
VMYEKAGHVITGLGIVGEVDGDDPAVFRPIQKYINGTWYNVAQV
STF118 accessory protein
(SEQ ID NO: 244)
MQHLKNITAGNPKTVAQYQLTKNFDVIWLWSEEGKNWYEEVSNFQEDTIKIVYDENNIIV
GITRDASTLNPEGFSVVEVPDITSNRRADDSGKWMFKDGAVIKRIYTADEQEQQAESQKA
ALLSEAESVILPLERAVRLNMATDEERSRLEAWERYSVLVSRVDPANPEWPEMPQ
K1
(SEQ ID NO: 245)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAADAKT
AAAGSASTASTKATEAAGSAVSASQSKSAAEAAAIRAKNSAKRAEDIASAVALEDADTTR
KGIVQLSSATNSTSETLAATPKAVKVVMDETNRKAPLDSPALTGTPTAPTALRGTNNTQI
ANTAFVLAAIADVIDASPDALNTLNELAAALGNDPDFATTMTNALAGKQPKNATLTALAG
LSTAKNKLPYFAENDAASLTELTQVGRDILAKNSVADVLEYLGAGENSGAKGDGVTDDTA
ALTSALNDTPVGQKINGNGKTYKVTSLPDISRFINTRFVYERIPGQPLYYASEEFVQGEL
FKITDTPYYNAWPQDKAFVYENVIYAPYMGSDRHGVSRLHVSWVKSGDDGQTWSTPEWLT
DLHPDYPTVNYHCMSMGVCRNRLFAMIETRTLAKNALTNCALWDRPMSRSLHLTGGITKA
ANQRYATIHVPDHGLFVGDFVNFSNSAVTGVSGDMTVATVIDKDNFTVLTPNQQTSDLNN
AGKNWHMGTSFHKSPWRKTDLGLIPSVTEVHSFATIDNNGFAMGYHQGDVAPREVGLFYF
PDAFNSPSNYVRRQIPSEYEPDASEPCIKYYDGVLYLITRGTRGDRLGSSLHRSRDIGQT
WESLRFPHNVHHTTLPFAKVGDDLIMFGSERAENEWEAGAPDDRYKASYPRTFYARLNVN
NWNADDIEWVNITDQIYQGGIVNSGVGVGSVVVKDNYIYYMFGGEDHFNPWTYGDNSAKD
PFKSDGHPSDLYCYKMKIGPDNRVSRDFRYGAVPNRAVPVFFDTNGVRTVPAPMEFTGDL
GLGHVTIRASTSSNIRSEVLMEGEYGFIGKSIPTDNPAGQRIIFCGGEGTSSTTGAQITL
YGANNTDSRRIVYNGDEHLFQSADVKPYNDNVTALGGPSNRFTTAYLGSNPIVTSNGERK
TEPVVFDDAFLDAWGDVHYIMYQWLDAVQLKGNDARIHFGVIAQQIRDVFIAHGLMDENS
TNCRYAVLCYDKYPRMTDTVFSHNEIVEHTDEEGNVTTTEEPVYTEVVIHEEGEEWGVRP
DGIFFAEAAYQRRKLERIEARLSALEQK
STF66
(SEQ ID NO: 246)
MAVKISGVLKDGTGKPVQNCTIQLKARRNSTTVVVNTVGSENPDEAGRYSMDVEYGQYSV
ILQVDGFPPSHAGTITVYEDSQPGTLNDFLCAMTEDDARPEVLRRLELMVEEVARNASVV
AQSTADAKKSAGDASASAAQVAALVTDATDSARAASTSAGQAASSAQEASSGAEAASAKA
TEAEKSAAAAESSKNAAATSAGAAKTSETNAAASQQSAATSASTAATKASEAATSARDAV
ASKEAAKSSETNASSSAGRAASSATAAENSARAAKTSETNARSSETAAERSASAAAASAT
AAANSQKAAKTSETNSKASETAAANSAKASAASQTAAKASEDAAREYASQAAEPYKQVLQ
PLPDVWIPFNDSLDMITGFSPSYKKIVIGDDEITMPGDKVVKFKRASKATYINKSGVLTE
AAIDEPRFERDGLLIEGQRTNYMLNSENPASWGRSSNMDVPETGTDSFGFTYGKFVCNDS
LIGQTSAINMASIAATKSVDVSGDNKYVTTSCRFKTELQVRLRIRFDKYDGSATTFLGDA
YIDTQTLEINMTGGASGRITARVRKDETTGWIFAEATIQAIDGELKIGSQIQYSPKQGGA
TVSGDYIYLATPQVENGACVSSFIISGTTAATRASDMVTIPTENNIYNRPLTCLVEVNRN
WGDIPPNVAPRIFDFSGVPPIESITYAFNTTEKYYGQLYMQTYKASTSSYVSSLFTGRTD
VRKLIGGFNIYSDGTKRVVSNGEATKTMKTEWTGVKTRTFIRIGGQATSGTRHLFGHLRN
LRLWHKELTDAQMGESIK
STF66 accessory protein
(SEQ ID NO: 247)
MKDLTLKFADRADFSAFMESIGYYDDESMQDDILIDVIGNVYKETGELTEDGEPVCVKED 
GYFVNVRIINDSQISSLFDEYVVAVEHQLRGWM 

Claims (26)

What is claimed is:
1. A method for treating a bacterial infection comprising administering to a subject having a bacterial infection in need of treatment the pharmaceutical or veterinary composition comprising a pharmaceutically acceptable carrier and one or more bacterial delivery vehicles comprising a chimeric receptor binding protein (RBP)
wherein the chimeric RBP comprises a fusion between the N-terminal domain of a RBP from a lambda-like or lambda bacteriophage, wherein said lambda-like bacteriophage comprises amino acid sequence homology of around 35% identity for 45 amino acids or more, around 50% identity for 30 amino acids or more, or around 90% identity for 18 amino acids or more in one or more of three amino acid regions ranging from positions 1-150, 320-460, and 495-560 with reference to the lambda bacteriophage stf sequence of SEQ ID NO: 1, and the C-terminal domain of a different RBP, and
wherein said N-terminal domain is fused to said C-terminal domain within one of the amino acids acid regions selected from positions 1-150, 320-460 or 495-560 of the N-terminal RBP with reference to the lambda stf sequence (SEQ ID NO: 1), wherein said region of fusion within the N-terminal RBP from positions 1-150, 320-460 or 495-560 comprises amino acid sequence homology of around 35% identity for 45 amino acids or more, around 50% identity for 30 amino acids or more, or around 90% identity for 18 amino acids or more with reference to the lambda bacteriophage stf sequence of SEQ ID NO: 1.
2. The method of claim 1, wherein said different RBP is derived from any bacteriophage or bacteriocin.
3. The method of claim 1, wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain within one of the amino acid regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP.
4. The method of claim 1, wherein the N-terminal domain and the C-terminal domain are fused within said region at an insertion site having at least 80% identity with insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
5. The method of claim 1, wherein the chimeric RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 123-129, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246.
6. The method of claim 1, wherein the C-terminal domain of the different RBP has a depolymerase activity against an encapsulated bacterial strain.
7. The method of claim 1, wherein the bacterial delivery vehicle further comprises a nucleic acid payload encoding a protein of interest or a nucleic acid of interest.
8. The method of claim 7, wherein the nucleic acid of interest is selected from the group consisting of Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor gene, a membrane protein gene, a structural protein gene, a secreted protein gene, a gene expressing resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any combination thereof.
9. The method of claim 8, wherein the enzyme is a nuclease or a kinase.
10. The method of claim 7, wherein the protein of interest is a nuclease that targets cleavage of a host bacterial cell genome or a host bacterial cell plasmid.
11. The method of claim 10, wherein the cleavage occurs in an antibiotic resistant gene.
12. The method of claim 7, wherein the nucleic acid payload encodes a therapeutic protein.
13. The method of claim 7, wherein the nucleic acid payload encodes an anti-sense nucleic acid molecule.
14. A method for reducing the amount of virulent and/or antibiotic resistant bacteria in a bacterial population comprising contacting the bacterial population with a bacterial delivery vehicle comprising a chimeric receptor binding protein (RBP), wherein the chimeric RBP comprises a fusion between the N-terminal domain of a RBP from a lambda-like or lambda bacteriophage, wherein said lambda-like bacteriophage comprises amino acid sequence homology of around 35% identity for 45 amino acids or more, around 50% identity for 30 amino acids or more, or around 90% identity for 18 amino acids or more in one or more of three amino acid regions ranging from positions 1-150, 320-460, and 495-560 with reference to the lambda bacteriophage stf sequence of SEQ ID NO: 1, and the C-terminal domain of a different RBP, and
wherein said N-terminal domain is fused to said C-terminal domain within one of the amino acids acid regions selected from positions 1-150, 320-460 or 495-560 of the N-terminal RBP with reference to the lambda stf sequence (SEQ ID NO: 1), wherein said region of fusion within the N-terminal RBP from positions 1-150, 320-460 or 495-560 comprises amino acid sequence homology of around 35% identity for 45 amino acids or more, around 50% identity for 30 amino acids or more, or around 90% identity for 18 amino acids or more with reference to the lambda bacteriophage stf sequence of SEQ ID NO: 1.
15. The method of claim 14, wherein said different RBP is derived from any bacteriophage or bacteriocin.
16. The method of claim 14, wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain within one of the amino acid regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP.
17. The method of claim 14, wherein the N-terminal domain and the C-terminal domain are fused within said region at an insertion site having at least 80% identity with insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
18. The method of claim 14, wherein the chimeric RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 123-129, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246.
19. The method of claim 14, wherein the C-terminal domain of the different RBP has a depolymerase activity against an encapsulated bacterial strain.
20. The method of claim 14, wherein the bacterial delivery vehicle further comprises a nucleic acid payload encoding a protein of interest or a nucleic acid of interest.
21. The method of claim 20, wherein the nucleic acid of interest is selected from the group consisting of Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor gene, a membrane protein gene, a structural protein gene, a secreted protein gene, a gene expressing resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any combination thereof.
22. The method of claim 21, wherein the enzyme is a nuclease or a kinase.
23. The method of claim 20, wherein the protein of interest is a nuclease that targets cleavage of a host bacterial cell genome or a host bacterial cell plasmid.
24. The method of claim 23, wherein the cleavage occurs in an antibiotic resistant gene.
25. The method of claim 20, wherein the nucleic acid payload encodes a therapeutic protein.
26. The method of claim 20, wherein the nucleic acid payload encodes an anti-sense nucleic acid molecule.
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